(R)-alpha-Methylhydrocinnamic acid [(2R)-2-Methyl-3-phenylpropanoic acid]

(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

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94 reactions in Reaxys

2018-07-27 00h:20m:47s (UTC)

OH

H

Search as: Product, As drawn, No mixtures ) AND (IDE.RN='14367-67-0') AND (IDE.INCHI='MCIIDRLDHRQKPHMRVPVSSYSA-N') NOT (RX.RXRN=2502292))

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

O

OH

O HO

H

HO

H

Rx-ID: 2062919 View in Reaxys 1/94 Yield

Conditions & References With hydrogen, <Rh2(COD)2><BF4>2, triethylamine in tetrahydrofuran, Time= 1h, p= 760Torr , Ambient temperature, different chiral catalysts, Product distribution Johnson, Thomas H.; Rangarajan, G.; Journal of Organic Chemistry; vol. 45; nb. 1; (1980); p. 62 - 65 View in Reaxys With hydrogen, di-μ-chlorobis(norbornadiene)dirhodium(I), chiral phosphinediamine in methanol, Time= 57h, T= 25 °C , p= 15001.2Torr , various solvents, pressures, times; other chiral phosphine diamine ligand, Product distribution Yamada, Issaku; Ohkouchi, Munetaka; Yamaguchi, Motowo; Yamagishi, Takamichi; Journal of the Chemical Society Perkin Transactions 1; nb. 12; (1997); p. 1869 - 1873 View in Reaxys With <RhCl(nbd)>2-(S,S)-isopropylbis<2-(1-N,N-dimethylaminoethyl)phenyl>phosphine, hydrogen in methanol, Time= 86h, T= 25 °C , p= 30400Torr , Title compound not separated from byproducts Yamada, Issaku; Yamaguchi, Motowo; Yamagishi, Takamichi; Tetrahedron Asymmetry; vol. 7; nb. 12; (1996); p. 3339 3342 View in Reaxys With hydrogen, di-μ-chlorobis(norbornadiene)dirhodium(I), (S,S)-isopropylbis<2-(1-N,N-dimethylaminoethyl)phenyl>phosphine in methanol, Time= 86h, T= 25 °C , p= 30002.4Torr , Yield given. Yields of byproduct given. Title compound not separated from byproducts Yamada, Issaku; Ohkouchi, Munetaka; Yamaguchi, Motowo; Yamagishi, Takamichi; Journal of the Chemical Society Perkin Transactions 1; nb. 12; (1997); p. 1869 - 1873 View in Reaxys With hydrogen, diacetato[(R)-(+)-2,2'-bis(diphenylphosphino)-5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyl]ruthenium(II) in methanol, Time= 48h, p= 1140Torr , Ambient temperature, Yield given. Yields of byproduct given. Title compound not separated from byproducts Uemura, Toshitsugi; Zhang, Xiaoyoung; Matsumura, Kazuhiko; Sayo, Noboru; Kumobayashi, Hidenori; Ohta, Tetsuo; Nozaki, Kyoko; Takaya, Hidemasa; Journal of Organic Chemistry; vol. 61; nb. 16; (1996); p. 5510 - 5516 View in Reaxys With hydrogen, [Ru(η2-O2CCH3)2((S)-H8-binap)] in methanol, Time= 48h, T= 25 °C , p= 1125.09Torr , Title compound not separated from byproducts Maienza, Francesca; Santoro, Francesco; Spindler, Felix; Malan, Christophe; Mezzetti, Antonio; Tetrahedron Asymmetry; vol. 13; nb. 16; (2002); p. 1817 - 1824 View in Reaxys With (S,S)-(-)-2,2'-bis[(R)-(N,N-dimethylamino)(phenyl)methyl]-1,1'-bis[di(3,5-dimethyl-4-methoxyphenyl)phosphine]ferrocene, hydrogen, di(norbornadiene)rhodium(I) tetrafluoroborate in methanol, Time= 94h, T= 25 °C , p= 37503Torr , Title compound not separated from byproducts Spindler, Felix; Malan, Christophe; Lotz, Matthias; Kesselgruber, Martin; Pittelkow, Ulrich; Rivas-Nass, Andreas; Briel, Oliver; Blaser, Hans-Ulrich; Tetrahedron Asymmetry; vol. 15; nb. 14; (2004); p. 2299 - 2306 View in Reaxys With (R)-1,1'-di[(3,4,5-Me3C6H2)2P]-9,9'-spirobifluorene*Ru(OAc)2, hydrogen in methanol, Time= 18h, T= 25 - 28 °C , p= 4560Torr , Title compound not separated from byproducts

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Cheng, Xu; Zhang, Qi; Xie, Jian-Hua; Wang, Li-Xin; Zhou, Qi-Lin; Angewandte Chemie - International Edition; vol. 44; nb. 7; (2005); p. 1118 - 1121 View in Reaxys With bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate, phosphoramidite based on chiral-3,3'-dimethylbinol, hydrogen, triphenylphosphine in water, isopropyl alcohol, Time= 16h, T= 30 °C , p= 18751.5Torr , Title compound not separated from byproducts Hoen, Rob; Boogers, Jeroen A. F.; Bernsmann, Heiko; Minnaard, Adriaan J.; Meetsma, Auke; Tiemersma-Wegman, Theodora D.; De Vries, Andre H. M.; De Vries, Johannes G.; Feringa, Ben L.; Angewandte Chemie - International Edition; vol. 44; nb. 27; (2005); p. 4209 - 4212 View in Reaxys With hydrogen, (R)-spirofluorene-[(3,4,5-Me3-C6H2)2P]2-[Ru(OAc)2] in methanol, Time= 18h, T= 25 - 28 °C , p= 4560Torr , Title compound not separated from byproducts Cheng, Xu; Xie, Jian-Hua; Li, Sheng; Zhou, Qi-Lin; Advanced Synthesis and Catalysis; vol. 348; nb. 10-11; (2006); p. 1271 - 1276 View in Reaxys With pyridylphosphorus ligand, zinc(II) salphen, hydrogen, di(norbornadiene)rhodium(I) tetrafluoroborate in dichloromethane, Time= 16h, T= 35 °C , p= 3750.3Torr , Product distribution, Further Variations: Reagents Kuil, Mark; Goudriaan, P. Elsbeth; Kleij, Arjan W.; Tooke, Duncan M.; Spek, Anthony L.; Van Leeuwen, Piet W. N. M.; Reek, Joost N. H.; Dalton Transactions; nb. 22; (2007); p. 2311 - 2320 View in Reaxys With hydrogen, triethylamine in methanol, Time= 65h, T= 25 °C , p= 4500.45Torr , Product distribution, Further Variations: Reagents Maienza, Francesca; Spindler, Felix; Thommen, Marc; Pugin, Benoit; Malan, Christophe; Mezzetti, Antonio; Journal of Organic Chemistry; vol. 67; nb. 15; (2002); p. 5239 - 5249 View in Reaxys With hydrogen, [1-[(1-Ph2P)Et]-2-(2-(3,5-(CF3)2-Ph)2-P-Ph)-ferrocene], rhodium in methanol, Time= 20h, T= 25 °C , p= 3750.38Torr , Product distribution, Further Variations: Catalysts Sturm, Thomas; Weissensteiner, Walter; Spindler, Felix; Advanced Synthesis and Catalysis; vol. 345; nb. 1-2; (2003); p. 160 - 164 View in Reaxys With hydrogen, [Ru(benzene)Cl]Cl in methanol, Time= 24h, T= 60 °C , p= 4500.45Torr , Title compound not separated from byproducts.

Qiu, Liqin; Li, Yue-Ming; Kwong, Fuk Yee; Yu, Wing-Yiu; Fan, Qing-Hua; Chan, Albert S. C.; Advanced Synthesis and Catalysis; vol. 349; nb. 4-5; (2007); p. 517 - 520 View in Reaxys C.12 :The catalyst precursor and the ligand were stirred in the solvent under argon. A solution of the substrate was added, the argon is drawn off with vacuum and the vessel is connected to a hydrogen supply at the given pressure and temperature. Switching on the stirrer starts the hydrogenation. After the given time, the stirrer is switched off and the solution is placed under argon again. Conversion and enantiomeric excess (ee) are determined by gas chromatography.

With hydrogen, bis(norbornadiene)rhodium(l)tetrafluoroborate, C40H58FeN2O3P2 in methanol, Time= 40h, T= 25 °C , p= 3750.38Torr , Product distribution / selectivity Patent; Solvias AG; WO2007/135179; (2007); (A1) English View in Reaxys With Johnson & Matthey type 440, hydrogen, cinchonidine, benzylamine in 1,4-dioxane, water, T= 23 °C , p= 760.051Torr , optical yield given as percent ee, enantioselective reaction Sugimura, Takashi; Uchida, Takayuki; Watanabe, Junya; Kubota, Takeshi; Okamoto, Yasuaki; Misaki, Tomonori; Okuyama, Tadashi; Journal of Catalysis; vol. 262; nb. 1; (2009); p. 57 - 64 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

With bis(norbornadiene)rhodium(l)tetrafluoroborate, hydrogen in tetrahydrofuran, Time= 24h, T= 20 °C , p= 7500.75Torr , optical yield given as percent ee, enantioselective reaction Lee, Jong-Dae; Thanh, Thien Co; Kim, Tae-Jeong; Sang, Ook Kang; Synlett; nb. 5; (2009); p. 771 - 774 View in Reaxys D.3 :0.41 g (2.53 mmol) of 2-methylcinnamic acid and 5 ml of degassed methanol are introduced in succession into a Schlenk vessel filled with argon. A catalyst solution consisting of 4.73 mg (0.01265 mmol) of [Rh(norbornadiene)2]BF4, 8.77 mg (0.0133 mmol) of ligand A and 5 ml of degassed methanol is prepared in a second Schlenk vessel filled with argon. This solution and the catalyst solution are then transferred in succession by means of a steel capillary into a 50 ml autoclave filled with argon.

The ratio of substrate/catalyst is 200. The autoclave is closed and a pressure of 5 bar is set by means of 4 flushing cycles (pressurization to 10 bar of hydrogen). The autoclave is thermostated at 25°C and the reaction is started by switching on the stirrer.

The reactor is stirred for 19 hours. After opening the autoclave, a reddish reaction solution is isolated. The conversion is quantitative (determined by means of GC and (at)H-NMR). Removal of the solvent on a rotary evaporator gives a quantitative yield of 2-methyl-3-phenylpropionic acid having an enantiomeric purity of 29percent ee (determined by means of HPLC after conversion into the methyl ester; column: Chiracel OB. ).

With hydrogen, bis(norbornadiene)rhodium(l)tetrafluoroborate, (S)-1-diphenylphosphino-2-[η-(S)-hydroxy-(o-diphenylphosphinophenyl)methyl]ferrocene in methanol, Time= 19h, T= 25 °C , p= 3750.38Torr , Product distribution / selectivity Patent; UMICORE AG and CO. KG; WO2005/108409; (2005); (A2) English View in Reaxys A method similar to that of Example D3 is employed. 8.96 mg (0.0133 mmol) of methoxy- TANIAPHOS are used in place of the ligand A. The conversion is 100percent. Removal of the solvent on a rotary evaporator gives a quantitative yield of 2-methyl-3-phenylpropionic acid having an enantiomeric purity of 30percent ee.

With hydrogen, bis(norbornadiene)rhodium(l)tetrafluoroborate, (S)-1-diphenylphosphino-2-[η-(S)-methoxy(o-diphenylphosphinophenyl)methyl]ferrocene in methanol, Time= 19h, T= 25 °C , p= 3750.38Torr , Product distribution / selectivity Patent; UMICORE AG and CO. KG; WO2005/108409; (2005); (A2) English View in Reaxys B.1 :The method of carrying out the hydrogenations and the determination of the optical yields ee is described in general terms

by W. Weissensteiner et al in Organometallics 21 (2002), pages 1766-1774. The catalysts are in each case prepared in situ in the solvent by mixing of the ligand and metal complex as catalyst precursor (unless indicated otherwise = [Rh(norbornadiene)2]BF4). Unless indicated otherwise, the substrate concentration is 0.25 mol/l. The determination of conversion and ee of MAA is carried out by means of gas chromatography using a chiral column (Chirasil-L-val).The hydrogenations of EAC are carried out in ethanol in the presence of 5percent (v/v) of CF3CH2OH. The determination of the ee is carried out by means of gas chromatography using a chiral column [Lipodex E (30m); 1300C isothermal; 190 KPa H2]. In the hydrogenation of EOV, [Rul2(p-cumene)]2 is used as metal complex and catalyst precursor. The determination of the ee is carried out after reaction with trifluoroacetic anhydride by means of gas chromatography using a chiral column [Lipodex E (30m)].In the hydrogenation of MEA, [Ir(COD)CI]2 is used as metal complex and catalyst precursor. The hydrogenation is carried out in bulk using 105 g of MEA (without solvent) in the presence of 70 mg of tetrabutylammonium iodide and 10 ml of acetic acid.

With hydrogen, bis(norbornadiene)rhodium(l)tetrafluoroborate, C62H78FeP4 in methanol, Time= 1h, T= 25 °C , p= 750.075Torr , Product distribution / selectivity Patent; SOLVIAS AG; WO2006/3195; (2006); (A1) English View in Reaxys B.1 :The method of carrying out the hydrogenations and the determination of the optical yields ee is described in general terms

by W. Weissensteiner et al in Organometallics 21 (2002), pages 1766-1774. The catalysts are in each case prepared in situ in the solvent by mixing of the ligand and metal complex as catalyst precursor (unless indicated otherwise = [Rh(norbornadiene)2]BF4). Unless indicated otherwise, the substrate concentration is 0.25 mol/l. The determination of conversion and ee of MAA is carried out by means of gas chromatography using a chiral column (Chirasil-L-val).The hydrogenations of EAC are carried out in ethanol in the presence of 5percent (v/v) of CF3CH2OH. The determination of the ee is carried out by means of gas chromatography using a chiral column [Lipodex E (30m); 1300C isothermal; 190 KPa H2]. In the hydrogenation of EOV, [Rul2(p-cumene)]2 is used as metal complex and catalyst precursor. The determination of the ee is carried out after reaction with trifluoroacetic anhydride by means of gas chromatography using a chiral column [Lipodex E (30m)].In the hydrogenation of MEA, [Ir(COD)CI]2 is used as metal complex and catalyst precursor. The hydrogenation is carried out in bulk using 105 g of MEA (without solvent) in the presence of 70 mg of tetrabutylammonium iodide and 10 ml of acetic acid.

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

With hydrogen, triethylamine, bis(norbornadiene)rhodium(l)tetrafluoroborate, C64H60FeN2P4 in tetrahydrofuran, Time= 1h, T= 25 °C , p= 3750.38Torr , Product distribution / selectivity Patent; SOLVIAS AG; WO2006/3195; (2006); (A1) English View in Reaxys With [Ru(CF3COO)2(1,5-COD)], (R,Rp)-2-[1-(dicyclohexylphosphinoethyl)]-1-[2-(diphenylphosphinomethyl)phenyl]ferrocene, hydrogen in methanol, Time= 2h, T= 25 °C , p= 15001.5Torr , enantioselective reaction Schuecker, Raffael; Mereiter, Kurt; Spindler, Felix; Weissensteiner, Walter; Advanced Synthesis and Catalysis; vol. 352; nb.

6; (2010); p. 1063 - 1074 View in Reaxys With hydrogen in tetrahydrofuran, Time= 16h, T= 20 °C , p= 5171.62Torr , Inert atmosphere, optical yield given as percent ee, enantioselective reaction Lee, Su Seong; Riduan, Siti Nurhanna; Erathodiyil, Nandanan; Lim, Jaehong; Cheong, Jian Liang; Cha, Junhoe; Han, Yu; Ying, Jackie Y.; Chemistry - A European Journal; vol. 18; nb. 24; (2012); p. 7394 - 7403 View in Reaxys With C56H36F12FeO10P2Ru4, hydrogen in ethanol, toluene, Time= 24h, T= 100 °C , p= 37503.8Torr , Autoclave, Reagent/catalyst, enantioselective reaction Moberg, Viktor; Duquesne, Robin; Roehrs, Oliver; Nachtigall, Jonny; Nordlander, Ebbe; Contaldi, Simone; Monari, Magda; Damoense, Llewellyn; Green, Michael; Hutton, Alan T.; Santelia, Daniela; Haukka, Matti; Chemistry--A European Journal; vol. 18; nb. 39; (2012); p. 12458 - 12478,21 View in Reaxys With C52H52FeO10P2Ru4, hydrogen in ethanol, toluene, Time= 24h, T= 100 °C , p= 37503.8Torr , Autoclave, enantioselective reaction Moberg, Viktor; Duquesne, Robin; Roehrs, Oliver; Nachtigall, Jonny; Nordlander, Ebbe; Contaldi, Simone; Monari, Magda; Damoense, Llewellyn; Green, Michael; Hutton, Alan T.; Santelia, Daniela; Haukka, Matti; Chemistry--A European Journal; vol. 18; nb. 39; (2012); p. 12458 - 12478,21 View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, (R)-1-{(RFc)-2-[2-(diphenylphosphino)phenyl]ferrocenyl}ethylbis[3,5-bis(trifluoromethyl)phenyl]phosphine, hydrogen in methanol, Time= 20h, T= 20 °C , p= 15201Torr , Autoclave, Reagent/catalyst Zirakzadeh, Afrooz; Gross, Manuela A.; Wang, Yaping; Mereiter, Kurt; Spindler, Felix; Weissensteiner, Walter; Organometallics; vol. 32; nb. 4; (2013); p. 1075 - 1084 View in Reaxys With di-μ-chlorobis(norbornadiene)dirhodium(I), (SFc)-2-((R)-1-diphenylphosphinoethyl)-(RFc)-2ηη-diphenylphosphino-1,1ηη-biferrocene, hydrogen in tetrahydrofuran, Time= 20h, T= 20 °C , p= 15201Torr , Autoclave, Catalytic behavior, Reagent/catalyst, Solvent Zirakzadeh, Afrooz; Gross, Manuela A.; Wang, Yaping; Mereiter, Kurt; Spindler, Felix; Weissensteiner, Walter; Organometallics; vol. 32; nb. 4; (2013); p. 1075 - 1084 View in Reaxys 3 : Example 3 Catalytic 6d Catalyzed Asymmetric Hydrogenation of α-Methyl Cinnamic Acid: In the glove box in an argon atmosphere,The catalyst 6d (3.6 mg) was added to a 5 mL hydrogenated vial and then the substrate η-methylcinnamic acid (32 mg, 0.2 mmol), triethylamine (22 mg, 0.2 mmol) and 1 mL of dichloromethane were added successively. The hydrogenated vials were placed in a hydrogenation reactor and the hydrogen was replaced three times and then filled with 30 atm H2 and reacted at room temperature for 4 h. After completion of the reaction, the reaction mixture was passed through a short silica gel column. 1HNMR was used to determine the conversion (81percent), and the enantioselective ee (81percent) of the reaction was determined by high performance liquid chromatography (HPLC).

With C49H66IrNOP(1+)*C32H12BF24 (1-), hydrogen, triethylamine in dichloromethane, Time= 4h, T= 20 °C , p= 22801.5Torr , Glovebox Patent; Wuhan Kaitelisi Technology Co., Ltd.; Zhang Xumu; Wang Qian; Dong Xiuqin; (12 pag.); CN106632478; (2017); (A) Chinese

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

View in Reaxys

O

O

OH

O HO

H

HO

H

Rx-ID: 29577152 View in Reaxys 2/94 Yield

Conditions & References With [Rh((R,R)-Cy-SMS-Phos)(MeOH)2]BF4, hydrogen, N-cyclohexyl-cyclohexanamine in methanol, Time= 3h, T= 20 °C , p= 7500.75Torr , optical yield given as percent ee Zupancic, Borut; Mohar, Barbara; Stephan, Michel; Organic Letters; vol. 12; nb. 13; (2010); p. 3022 - 3025 View in Reaxys 5 :The chiral catalyst [Show Image] is used, the asymmetric catalytic hydrogenation of 2- benzyl acrylic acid 7 is carried out under the condition same to that of Embodiment 5, the result of the reaction is that: the conversion rate is 100percent, the yield is 93percent and the ee value of the product is 73percent.

Stage 1: With hydrogen, caesium carbonate, [(Sa-DTB-SIPHOX)Ir(COD)]BARF in methanol, Time= 12h, T= 20 °C , p= 4500.45Torr Stage 2: With hydrogenchloride in water, pH= < 3, Product distribution / selectivity Patent; Zhejiang Jiuzhou Pharmaceutical Co., Ltd.; EP2272853; (2011); (A1) English View in Reaxys With di(norbornadiene)rhodium(I) tetrafluoroborate, C33H48FeNP2, hydrogen in ethanol, Time= 5h, T= 20 °C , p= 760.051Torr , Resolution of racemate Patent; Wuhan Science and Technology Co., Ltd.; Zhang, Xumu; Chen, Caiyou; (17 pag.); CN105481909; (2016); (A) Chinese View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, C33H47FeNP2, hydrogen in ethanol, Time= 6h, T= 20 °C , p= 750.075Torr Chen, Caiyou; Wang, Heng; Zhang, Zhefan; Jin, Shicheng; Wen, Songwei; Ji, Jianjian; Chung, Lung Wa; Dong, XiuQin; Zhang, Xumu; Chemical Science; vol. 7; nb. 11; (2016); p. 6669 - 6673 View in Reaxys

O

OH O

O

HO

H HO

HO

HO

H OH

Rx-ID: 44747951 View in Reaxys 3/94 Yield 48 %

Conditions & References With acetobacter aceti culture medium containing glucose, yeast extract, agar, glycerol and distilled wateracetobacter aceti, Time= 72h, Microbiological reaction Brenna, Elisabetta; Cannavale, Flavia; Crotti, Michele; De Vitis, Valerio; Gatti, Francesco G.; Migliazza, Gaia; Molinari, Francesco; Parmeggiani, Fabio; Romano, Diego; Santangelo, Sara; ChemCatChem; vol. 8; nb. 24; (2016); p. 3796 - 3803 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

O

O

OH

N

N

H

O

Pol (v1)

Rx-ID: 44204007 View in Reaxys 4/94 Yield

Conditions & References

55 %

4 :10 ml of dioxane is added to a 50 ml round-bottomed flask containing compound 6A (0.05 g, 1 eq), and 10 ml of 2N NaOH is slowly added thereto. After refluxing at 100 ° C for 2 hours, it was extracted with dichloromethane. To the extracted dichloromethane solution was added saturated ammonium chloride and extracted with dichloromethaneThe organic layer was dried with magnesium sulfate and then precipitated in about 200 ml of methanol cooled to -78 ° C. The precipitated solution was filtered and the filtered solid was washed with a mixed solution of methanol and distilled water in a volume ratio of 1: 1. The solid remaining in the filter was then taken to yield compound 4A.The water layer was acidified (pH 2-3) with hydrogen chloride and extracted with ethyl acetate. The organic layer extracted with ethylacetate was dried over magnesium sulfate and purified by column chromatography (eluent: ethyl acetate: n-hexane + 2: 8) to obtain compound 8A. Table 3 below shows the results of measurement of enantiomeric excess of Compound 8A using HPLC (eluent: 2-propanol: n-hexane = 5: 95).

With sodium hydroxide in 1,4-dioxane, water Solid phase= non-crosslinked chloromethylated polystyrene, Time= 2h, T= 100 °C Patent; Chonnam National Academic Foundation; Kim, Taek Hyun; Kang, Byung Sun; (19 pag.); KR2015/105875; (2015); (A) Korean View in Reaxys

O

OH

H

Rx-ID: 7625855 View in Reaxys 5/94 Yield 99%

Conditions & References 12 :General procedure: [0068] The catalyst (S)-5a (0.9mg, 0.0005mmol), alpha-substituted acrylic acid 6 (0.5mmol) and cesium carbonate (82mg, 0.25mmol) were weighed from glove box and transferred into the reaction inner tube containing a stir bar. The tube was sealed as a spare. Methanol (2mL) was injected into the tube with syringe after fetching out the tube. The inner tube was placed in the hydrogenation reaction still. The original atmosphere was displaced with hydrogen atmosphere by inflatingdeflating operation (3-5 times). The hydrogen pressure was ultimately set at 0.6MPa. At the temperature of 45 , the reaction was proceeded with stirring until the pressure stopped decreasing. After stopping stirring to release hydrogen and concentrating the system with rotary steaming, the pH value of the system was adjusted with 3 N hydrochloric acid until pH 3). The organic phases merged together were washed by sodium chloride solution and dried by anhydrous sodium sulfate. The drying agent was removed by suction filtration. The target product (R) 7 was obtained after solvent was removed by rotary steaming. The conversion rate was analyzed by 1H NMR proving that all of the reactions were converted completely. The ee value was analyzed by chiral GC, chiral HPLC or chiral SFC after the product was transformed into corresponding methyl ester. The experimental results determined are listed in Table 6 With C54H68IrNP(1+)*C32H12BF24 (1-), hydrogen, caesium carbonate in methanol, Time= 0.25h, T= 45 °C , p= 4500.45Torr , Glovebox, Sealed tube Patent; Zhejiang Jiuzhou Pharmaceutical Co., Ltd.; ZHOU, Qilin; ZHU, Shoufei; YU, Yanbo; LI, Kun; WANG, Lixin; EP2752419; (2014); (A1) English View in Reaxys

91%

19 : EXAMPLE 19 STR45 EXAMPLE 19 STR45

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

A 10 mL recovery flask equipped with a magnetic stirrer was charged with [1S-[1R*(S*), 2R*]]-N-(2-hydroxy-1-methyl-2-phenylethyl)-N,2-dimethyl benzenepropion amide (75 mg, 0.24 mmol, 1.0 equiv) and a mixture of tetrabutylammonium hydroxide (0.78g of a 40percent aqueous solution, 1.21 mmol, 5 equiv) in 4:1 water: tert-butanol (5 mL), and the resulting mixture was refluxed for 22 h under a Liebig condenser.

The reaction mixture was basified with 1N sodium hydroxide (100 mL), and extracted with ether (3*10 mL).

The aqueous phase was acidified with 3N HCl, saturated with sodium chloride, and extracted with ethyl acetate (3*15 mL).

The combined ethyl acetate extracts were washed once with water (5 mL), dried over sodium sulfate, filtered, and concentrated to give R-η-methyl benzenepropionic acid (36 mg, 91percent yield) with an enantiomeric excess of 94percent (as determined by chiral GC analysis of the R-η-methylbenzyl amide of the acid).

1H NMR (300 MHz, CDCl3)η7.25 (m, 5H), 3.09 (dd, 1H, J1=6.1 Hz, J2=13.1 Hz), 2.75 (m, 2H, H), 1.18 (d, 3H, J=6.8 Hz); 13C NMR (75.5 MHz, CDCl3)η182.5, 139.0, 129.0, 128.4, 126.4, 41.2, 39.3, 16.5; FTIR (neat film) cm-1 2976 (s,br, OH), 2657 (m, br), 1948 (w), 1877 (w), 1806 (w), 1707 (s, C=O), 1496 (m), 1454 (s), 1417 (m), 1294 (s), 1241 (s), 1117 (w), 1082 (w), 942 (m), 744 (m), 700 (s), 549 (w).

Patent; California Institute of Technology; US5488131; (1996); (A) English View in Reaxys 87%

18 : R-α-methyl benzenepropionic acid EXAMPLE 18 STR44 R-η-methyl benzenepropionic acid A 50 mL round-bottomed flask was charged with [1S-[1R*(S*), 2R*]]-N-(2-hydroxy-1-methyl-2-phenylethyl)-N,2-dimethyl benzenepropion amide (1.2458g, 4.0 mmol) and 10:8 18N sulfuric acid: dioxane (18 mL).

The resulting mixture was refluxed for 1 h under a Liebig condenser.

The mixture was then basified with 50percent aqueous sodium hydroxide, and washed with dichloromethane (2*50 mL).

The remaining aqueous phase was acidified with 6N aqueous sulfuric acid and extracted with dichloromethane (3*50 mL).

These extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford R-η-methyl benzenepropionic acid (0.5719 g, 87percent yield) with an enantiomeric excess of 97percent (as determined by chiral GC analysis of the R-η-methylbenzyl amide of the acid).

Patent; California Institute of Technology; US5488131; (1996); (A) English View in Reaxys

81%

8 : Preparation of Some Representative Intermediates for the Elaboration of the N-Terminus of the Compound of Formula 1 To a cooled solution (0°) of the latter oxazolidine derivative (26.7 g, 97.0 mmol) in THF (9500 mL) and H2 O (1.5 L) was added a 30percent aqueous solution of hydrogen peroxide (55 mL, 0.5 mol), followed by the addition of a solution of LiOH.H2 O (8.67 g, 200 mmol) in H2 O (15 mL).

The resultant mixture was vigorously stirred for 1 h at 0°.

A solution of Na2 SO3 (100 g) in H2 O (700 mL) and solid NaHCO3 (20 g) were added sequentially.

After 5 min, the THF was removed under reduce pressure.

The residual aqueous solution was washed with CH2 Cl12 (3 X).

The aqueous phase was rendered acidic with 10percent aqueous HCl1 and extracted with Et2 O (3 X).

The combined Et2 O extracts were washed with brine, dried (MgSO4) and concentrated to afford η(R)-methylbenzenepropionic acid as a clear liquid (12.8 g, 81percent yield).

1 H NMR (CDCl ) η 7.33-7.19 (m, 5H), 3.10 (dd, J=13.5, 6.5, 1H), 2.83-2.74 (m, 1H), 2.79 (dd, J=13.5, 8 Hz, 1H), 1.20 (d, J=7 3 Hz, 3H).

Patent; Bio-Mega/Boehringer Ingelheim Research, Inc.; US5672586; (1997); (A) English View in Reaxys Meyers,A.I. et al.; Heterocycles; vol. 6; (1977); p. 971 - 977 View in Reaxys Valentine; Scott; Synthesis; (1978); p. 329,343 View in Reaxys Bezmer; Brown; Journal of Pharmaceutical Sciences; vol. 60; (1971); p. 583,584 View in Reaxys 8 : EXAMPLE 8 This acid was combined with 18.4 g of d-(+)-η-methylbenzylamine in 160 ml of ethyl acetate, dissolved by heating on a steam bath, cooled, and the precipitate was collected to yield 35 g of the amine salt.

After three additional recrystallizations from ethyl acetate, the amine salt (0.4 g) was treated with 100 ml of 1M sulfuric acid.

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The aqueous layer was extracted with chloroform (2*100 ml) and the combined organic extracts dried over magnesium sulfate, filtered and concentrated.

The residue was purified by radial chromatography (5percent methanol in chloroform, 2 mm plate) to yield 186 mg of (R)-2benzylpropionic acid.

Patent; Merrell Pharmaceuticals Inc.; US5840729; (1998); (A) English View in Reaxys 8 : EXAMPLE 8 This acid was combined with 18.4 g of d-(+)-η-methylbenzylamine in 160 ml of ethyl acetate, dissolved by heating on a steam bath, cooled, and the precipitate was collected to yield 35 g of the amine salt.

After three additional recrystallizations from ethyl acetate, the amine salt (0.4 g) was treated with 100 ml of 1M sulfuric acid.

The aqueous layer was extracted with chloroform (2 x 100 ml) and the combined organic extracts dried over magnesium sulfate, filtered and concentrated.

The residue was purified by radial chromatography (5percent methanol in chloroform, 2 mm plate) to yield 186 mg of (R)-2benzylpropionic acid.

Patent; Merrell Dow Pharmaceuticals Inc.; US5047534; (1991); (A) English View in Reaxys

O

O

OH

O HO

H

HO

H

Rx-ID: 28260217 View in Reaxys 6/94 Yield

Conditions & References D.3 :0.41 g (2.53 mmol) of 2-methylcinnamic acid and 5 ml of degassed methanol are introduced in succession into a Schlenk vessel filled with argon. A catalyst solution consisting of 4.73 mg (0.01265 mmol) of [Rh(norbornadiene)2]BF4, 8.77 mg (0.0133 mmol) of ligand A and 5 ml of degassed methanol is prepared in a second Schlenk vessel filled with argon. This solution and the catalyst solution are then transferred in succession by means of a steel capillary into a 50 ml autoclave filled with argon. The ratio of substrate/catalyst is 200. The autoclave is closed and a pressure of 5 bar is set by means of 4 flushing cycles (pressurization to 10 bar of hydrogen). The autoclave is thermostated at 25° C. and the reaction is started by switching on the stirrer. The reactor is stirred for 19 hours. After opening the autoclave, a reddish reaction solution is isolated. The conversion is quantitative (determined by means of GC and 1H-NMR). Removal of the solvent on a rotary evaporator gives a quantitative yield of 2-methyl-3-phenylpropionic acid having an enantiomeric purity of 29percent ee (determined by means of HPLC after conversion into the methyl ester; column: Chiracel OB.).

With hydrogen, (S)-1-diphenylphosphino-2-[η-(S)-hydroxy-(o-diphenylphosphinophenyl)methyl]ferrocene, [Rh(norbornadiene)2]BF4 in methanol, Time= 19h, T= 25 °C , p= 7500.75Torr , Product distribution / selectivity Patent; Lotz, Matthias; Spindler, Felix; US2008/287698; (2008); (A1) English View in Reaxys D.3 :A method similar to that of Example D3 is employed. 8.96 mg (0.0133 mmol) of methoxy-, TANIAPHOS are used in place of the ligand A. The conversion is 100percent. Removal of the solvent on a rotary evaporator gives a quantitative yield of 2methyl-3-phenylpropionic acid having an enantiomeric purity of 30percent ee.

With hydrogen, (S)-1-diphenylphosphino-2-[η-(S)-methoxy(o-diphenylphosphinophenyl)methyl]ferrocene, [Rh(norbornadiene)2]BF4 in methanol, Time= 19h, T= 25 °C , p= 7500.75Torr , Product distribution / selectivity Patent; Lotz, Matthias; Spindler, Felix; US2008/287698; (2008); (A1) English View in Reaxys With diphenyl{1-[(S)-2,6-bis-trimethylsilyl-3,5-dioxa-4-phospha-cyclohepta(2,1-a;3,4-a')dinaphthalen-4-yl]-3-methyl-2-indolyl}phosphine, bis(norbornadiene)rhodium(l)tetrafluoroborate, hydrogen in dichloromethane, Time= 20h, T= 20 °C , p= 7500.75Torr , Inert atmosphere, optical yield given as percent ee Wassenaar, Jeroen; Kuil, Mark; Reek, Joost N. H.; Advanced Synthesis and Catalysis; vol. 350; nb. 10; (2008); p. 1610 1614

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View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, (S(p),S(p))-2,2''-bis(diphenylphosphino)-1,1''-biferrocene, hydrogen in methanol, Time= 15h, T= 25 °C , p= 3750.38Torr , Autoclave, optical yield given as percent ee, enantioselective reaction Espino, Gustavo; Xiao, Li; Puchberger, Michael; Mereiter, Kurt; Spindler, Felix; Manzano, Blanca R.; Jalon, Felix A.; Weissensteiner, Walter; Dalton Transactions; nb. 15; (2009); p. 2751 - 2763 View in Reaxys With 5% Pd(II)/C(eggshell), Cinchonidin in 1,4-dioxane, water, T= 22.84 °C , optical yield given as percent ee, enantioselective reaction Sugimura, Takashi; Ogawa, Hiroyuki; Chemistry Letters; vol. 39; nb. 3; (2010); p. 232 - 233 View in Reaxys With 5% Pd(II)/C(eggshell), Cinchonin in 1,4-dioxane, water, T= 22.84 °C , optical yield given as percent ee, enantioselective reaction Sugimura, Takashi; Ogawa, Hiroyuki; Chemistry Letters; vol. 39; nb. 3; (2010); p. 232 - 233 View in Reaxys With diisopropyl{1-[(S)-2,6-dimethyl-3,5-dioxa-4-phospha-cyclohepta(2,1-a;3,4-a')dinaphthalen-4-yl]-3-methyl-2-indolyl}phosphine, bis(norbornadiene)rhodium(l)tetrafluoroborate, hydrogen in dichloromethane, Time= 16h, T= 25 °C , p= 7500.75Torr , optical yield given as percent ee, enantioselective reaction Wassenaar, Jeroen; Kuil, Mark; Lutz, Martin; Spek, Anthony L.; Reek, Joost N. H.; Chemistry - A European Journal; vol.

16; nb. 22; (2010); p. 6509 - 6517 View in Reaxys 1.5 :Embodiment 1: Asymmetric catalytic hydrogenation of η- methyl cinnamic acid [Show Image] In the glove box, the catalyst (0.00125 mmol) and η- methyl cinnamic acid 1a (81 mg, 0.5 mmol) are weighted in the reaction inner tube with stirring bar, then the reaction inner tube is sealed for use. When the reaction inner tube is took out, the additive and the solvent are added, then the inner tube is placed into the hydrogenation reactor, the mixture is stirred under the hydrogen pressure of 0.6~10 Mpa till the pressure stops declining. Then the stirring is stopped, the hydrogen is released. After the system is condensed by evaporating off rotatably, the system is adjusted pH <3 with 3N hydrochloric acid water solution, extracted with diethyl ether (10 mL .x. 3), and separated, the organic phase is collected, washed with saturated salt water, and dried with anhydrous sodium sulfate. The desiccant is removed by suction filtration, the solvent is evaporated off by rotating, then the object product 2a is obtained. The conversion rate is analyzed through 1H NMR, after it is converted to amide, its ee value is analyzed through the chiral HPLC analysis.

The experimental results obtained are shown in Table 1: With hydrogen, C32H12BF24 (1-)*C43H42IrNOP(1+) in methanol, T= 20 °C , p= 4500.45Torr , Sealed tube, Product distribution / selectivity Patent; Zhejiang Jiuzhou Pharmaceutical Co., Ltd.; EP2275398; (2011); (A1) English View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, C53H50O5P2, hydrogen in dichloromethane, Time= 12h, T= 20 °C , p= 30003Torr , Inert atmosphere, optical yield given as percent ee, enantioselective reaction Robert, Tobias; Abiri, Zohar; Sandee, Albertus J.; Schmalz, Hans-Guenther; Reek, Joost N.H.; Tetrahedron Asymmetry; vol. 21; nb. 21-22; (2010); p. 2671 - 2674 View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, (3aR,8aR)-6-((3-(diphenylphosphanyl)[1,1'-biphenyl]-2-yl)oxy)-2,2-dimethyl-4,4,8,8-tetraphenyltetrahydro[1,3]dioxolo[4,5-e][1,3,2]dioxaphosphepine, hydrogen in dichloromethane, Time= 12h, T= 20 °C , p= 30003Torr , Inert atmosphere, optical yield given as percent ee, enantioselective reaction Robert, Tobias; Abiri, Zohar; Sandee, Albertus J.; Schmalz, Hans-Guenther; Reek, Joost N.H.; Tetrahedron Asymmetry; vol. 21; nb. 21-22; (2010); p. 2671 - 2674 View in Reaxys With 1% Pd/η-Al2O3, hydrogen, Time= 4h, T= 20 °C , p= 760.051Torr , enantioselective reaction Sun, Xiaojing; Williams, Christopher T.; Catalysis Communications; vol. 17; (2012); p. 13 - 17 View in Reaxys

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With (η4-1,5-cyclooctadiene)(1-[(4S)-(2-(1-adamantyl)-4,5-dihydrooxazolyl)ethyl]-3-(2,6-diisopropylphenyl)-4,5-dihydroimidazolin-2-ylidene)iridium(I) tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, hydrogen in dichloromethane, Time= 16h, T= 25 °C , p= 37503.8Torr , Reagent/catalyst, enantioselective reaction Khumsubdee, Sakunchai; Fan, Yubo; Burgess, Kevin; Journal of Organic Chemistry; vol. 78; nb. 19; (2013); p. 9969 - 9974 View in Reaxys With 5% palladium on Al2O3, hydrogen, cinchonidine in N,N-dimethyl-formamide, Kinetics, Solvent, Reagent/catalyst, Optical yield = 17 percent ee; enantioselective reaction Sun, Xiaojing; Monnier, John R.; Williams, Christopher T.; Catalysis Letters; vol. 143; nb. 9; (2013); p. 881 - 886 View in Reaxys General procedure for hydrogenation General procedure: Hydrogenation was carried out in a magnetically stirred autoclave in 1,4-dioxane containing 2.5percent (v/v) of water under an atmospheric pressure of hydrogen at room temperature. The catalyst (20mg) was pre-treated in a H2 flow at 375°C for 30min. After cooling down and transferred to the autoclave, the catalyst was pre-treated with modifier CD (0.02mmol) in 4mL solvent for an additional 30min. Then, certain amount of substrate and BA, as an effective additive, in 2mL solvent were added to the mixture. After adjusting the hydrogen pressure to the desired H2 pressure, the stirring was started. For substrates 1–4, the mixture after reaction was first neutralized with a diluted HCl solution, extracted with ethyl ether and analyzed by hydrogen nuclear magnetic resonance (1H NMR, Bruker DRX 400MHz type spectrometer) for conversion and a high performance liquid chromatography (HPLC, 6890 Agilent Co.) equipped with a chiral column (Daicel Chiralcel OJ-H) for enantiomeric excess (ee). For substrates 5 and 6, the mixture after reaction was first neutralized with a diluted HCl solution. Then, the catalyst and liquid were separated by centrifugation. After passing the liquid phase through a short silica column and drying, the conversion and enantioselectivity of 5 or 6 were determined on a gas chromatograph (Agilent 6890, 30m×0.32mm×0.25μm HP19091G-B213 capillary column).

With cinchonidine, 5% Pd/CNT, hydrogen, benzylamine in 1,4-dioxane, water, p= 750.075Torr , Catalytic behavior, Reagent/ catalyst, enantioselective reaction Guan, Zaihong; Lu, Shengmei; Li, Can; Journal of Catalysis; vol. 311; (2014); p. 1 - 5 View in Reaxys 4.7.2. Condition B (for acid substrates).

General procedure: For monodentate ligand study; Ir(COD)2BARF or Rh(COD)2BARF (3 molpercent) and appropriate monodentate ligand (6.6 molpercent) were dissolved in MeOH (0.5 M). The mixture was stirred for 15 min, then corresponding unsaturated acid (0.25 mmol) and Cs2CO3 (0.13 mmol) were added to the mixture. The resulting mixture was degassed by three cycles of freeze–pump–thaw and then transferred to a Parr bomb. The bomb was pressurized to 50 bar with hydrogen and the mixture was stirred at 300 rpm for 16 h. The bomb was then vented and solvent was evaporated. The crude product was passed through a short silica plug using 30 percent EtOAc/hexanes as the eluant. The enantiomeric ratio was then measured through chiral GC analysis.

With [Ir(cycloocta-1,5-diene)2](tetrakis(3,5-bis(trifluoromethyl)phenyl)borate), (1S,2S,4S,5R)-2-((1R)-(dinaphtho[2,1-d:1',2'-f] [1,3,2]dioxaphosphepin-4-yloxy)(6-methoxyquinolin-4-yl)methyl)-5-vinylquinuclidine, hydrogen, caesium carbonate in methanol, Time= 24h, T= 25 °C , p= 37503.8Torr , Reagent/catalyst, enantioselective reaction Khumsubdee, Sakunchai; Burgess, Kevin; Tetrahedron; vol. 70; nb. 6; (2014); p. 1326 - 1335 View in Reaxys With bis(norbornadiene)rhodium(l)tetrafluoroborate, (Sp)-2-{(R)-1-bis[3,5-bis(trifluoromethyl)phenyl]phosphinoethyl}-(Sp)-2ηdiphenylphosphino-1,1η-biferrocene, hydrogen in methanol, Time= 20h, T= 20 °C , p= 37503.8Torr , Inert atmosphere, Autoclave Zirakzadeh, Afrooz; Gross, Manuela A.; Wang, Yaping; Mereiter, Kurt; Weissensteiner, Walter; Organometallics; vol. 33; nb. 8; (2014); p. 1945 - 1952 View in Reaxys Stage 1: With bis(norbornadiene)rhodium(l)tetrafluoroborate, (R)-1-[2-(2'-diphenylphosphinophenyl)-ferrocenyl]ethyldi[bis-(3,5-trifluoromethyl)phenyl]phosphine, hydrogen in methanol, Time= 20h, T= 20 °C , p= 37503.8Torr , Inert atmosphere, Autoclave Stage 2: With hydrogen in methanol, Time= 16h, T= 20 °C , p= 15001.5Torr , Autoclave

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Zirakzadeh, Afrooz; Gross, Manuela A.; Wang, Yaping; Mereiter, Kurt; Weissensteiner, Walter; Organometallics; vol. 33; nb. 8; (2014); p. 1945 - 1952 View in Reaxys

O

O

HO

OH

H

Rx-ID: 30020624 View in Reaxys 7/94 Yield 99 %

Conditions & References 12 : Hydrogenation of Alpha-Substituted Acrylic Acid at the Hydrogen Pressure of 0.6 MPa General procedure: Example 12 Hydrogenation of Alpha-Substituted Acrylic Acid at the Hydrogen Pressure of 0.6 MPa The catalyst (S)-5a (0.9 mg, 0.0005 mmol), alpha-substituted acrylic acid 6 (0.5 mmol) and cesium carbonate (82 mg, 0.25 mmol) were weighed from glove box and transferred into the reaction inner tube containing a stir bar. The tube was sealed as a spare.

Methanol (2 mL) was injected into the tube with syringe after fetching out the tube. The inner tube was placed in the hydrogenation reaction still. The original atmosphere was displaced with hydrogen atmosphere by inflating-deflating operation (3-5 times).

The hydrogen pressure was ultimately set at 0.6 MPa. At the temperature of 45, the reaction was proceeded with stirring until the pressure stopped decreasing. After stopping stirring to release hydrogen and concentrating the system with rotary steaming, the pH value of the system was adjusted with 3 N hydrochloric acid until pH<3. The mixture was extracted by ether (10 mL 3). The organic phases merged together were washed by sodium chloride solution and dried by anhydrous sodium sulfate. The drying agent was removed by suction filtration. The target product (R) 7 was obtained after solvent was removed by rotary steaming.

The conversion rate was analyzed by 1H NMR proving that all of the reactions were converted completely. The ee value was analyzed by chiral GC, chiral HPLC or chiral SFC after the product was transformed into corresponding methyl ester. The experimental results determined are listed in Table 6.

With C54H72IrNP(1+)*C32H12BF24 (1-), hydrogen, caesium carbonate in methanol, Time= 0.25h, T= 45 °C , p= 4500.45Torr , Glovebox, Pressure Patent; ZHEJIANG JIUZHOU PHARMACEUTICAL CO., LTD.; Zhou, Qilin; Zhu, Shoufei; Yu, Yanbo; Li, Kun; Wang, Lixin; US2014/194638; (2014); (A1) English View in Reaxys

98 %

With C32H12BF24 (1-)*C54H71IrNP(1+), hydrogen, caesium carbonate in methanol, Time= 4h, T= 45 °C , optical yield given as percent ee, enantioselective reaction Zhu, Shou-Fei; Yu, Yan-Bo; Li, Shen; Wang, Li-Xin; Zhou, Qi-Lin; Angewandte Chemie - International Edition; vol. 51; nb.

35; (2012); p. 8872 - 8875 View in Reaxys

94 %

5 :In the glove box, the catalyst [(Sa-DTB-SIPHOX)Ir(COD)]BARF 4 (2.4 mg, 0.00125 mmol) , 2- benzyl acrylic acid 7 (81 mg, 0.5 mmol) and cesium carbonate (82 mg, 0.25 mmol) are weighted in the reaction inner tube with stirring bar, then the reaction inner tube is sealed for use. When the reaction inner tube is took out, anhydrous methanol (2 mL) is added with a syringe, then the inner tube is placed into the hydrogenation reactor, the mixture is stirred at room temperature under the hydrogen pressure of 0.6 Mpa to react for 12 h. Then the stirring is stopped, the hydrogen is released. After the system is condensed by evaporating off rotatably, the system is adjusted pH <3 with 3N hydrochloric acid water solution, extracted with diethyl ether (10 mL .x. 3), and separated, the organic phase is collected, washed with saturated salt water, and dried with anhydrous sodium sulfate. The desiccant is removed by suction filtration, the solvent is evaporated off by rotating, then the object product 8 is obtained, and is a colorless oily liquid, through the 1H NMR analysis, the conversion rate is 100percent and the yield is 94percent.[η]30,D -31.9 (c 1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3): η 9.95 (brs, 1H, COOH), 7.31-7.18 (m, 5H, Ar-H), 3.08 (dd, J = 13.2 and 6.4 Hz, 1H, CH2), 2.77 (sextet, J = 6.8 Hz, 1H, CH), 2.67 (dd, J = 13.2 and 8.0 Hz, 1H, CH2), 1.18 (d, J = 6.8 Hz, 3H, CH3); after it is converted to phenyl amide, its ee value is 91 percent through the chiral SFC analysis.

Stage 1: With hydrogen, caesium carbonate, [(Sa-DTB-SIPHOX)Ir(COD)]BARF in methanol, Time= 12h, T= 20 °C , p= 4500.45Torr Stage 2: With hydrogenchloride in water, pH= < 3, Product distribution / selectivity Patent; Zhejiang Jiuzhou Pharmaceutical Co., Ltd.; EP2272853; (2011); (A1) English View in Reaxys

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O

OH

O

H O

N

Rx-ID: 36840260 View in Reaxys 8/94 Yield

Conditions & References Reaction Steps: 2 1: lithium hydroxide; dihydrogen peroxide / tetrahydrofuran; water / 0.83 h / 0 °C 2: hydrogenchloride / water / 6 h / 60 - 110 °C With hydrogenchloride, dihydrogen peroxide, lithium hydroxide in tetrahydrofuran, water Garduno-Castro, Monserrat H.; Hernandez-Rodriguez, Marcos; Tetrahedron Letters; vol. 55; nb. 1; (2014); p. 193 - 196 View in Reaxys

O O

OH

HN H

Rx-ID: 36840288 View in Reaxys 9/94 Yield

Conditions & References General procedure for auxiliary removal General procedure: To a solution of 14.3 mg (0.6 mmol, 2equiv) LiOH in 3.24 ml THF:H2O (1:1) was added 68 mg (0.6 mmol, 4equiv.) of H2O2 30percent and stirred for 3 min. It was cooledto 0 °C and then added to a solution (at 0°C) with 0.3 mmol (1 equiv.) of thealkylated amide in 3.24 mL of THF. It was stirred 50 min. at 0°C. It was added151 mg (1.2 mmol, 4 equiv.) of Na2SO3 in 1.8 mL of water andstirred 5 min. It was extracted with AcOEt, washed with NaHCO3,dried and concentrated. The residue was suspended in 1 mL of HCl conc. andheated in oil bath 1 h at 60°C, 1 h (60 to 90°C), 1 h at 90°C, 2 h 100°C and 1hat 110°C. It was diluted with 10 mL of CH2Cl2 and added10 mL of sodium bicarbonate saturated aqueous solution. The aqueous solutionwas acidified with HCl (conc.) and extracted with CH2Cl2(15 mL X 2), the combined organic layers were dried and concentrated (NOTE: donot use hi-vaccum).

With hydrogenchloride in water, Time= 6h, T= 60 - 110 °C Garduno-Castro, Monserrat H.; Hernandez-Rodriguez, Marcos; Tetrahedron Letters; vol. 55; nb. 1; (2014); p. 193 - 196 View in Reaxys

O

OH

O

O

H

HO

H

Rx-ID: 37944484 View in Reaxys 10/94 Yield

Conditions & References With aldehyde dehydrogenase from pseudomonas putida KT2440, ene reductase from gluconobacter oxydans, water, NADPH in aq. buffer, Time= 24h, T= 25 °C , pH= 6.2, Enzymatic reaction, Optical yield = 64 percent ee; enantioselective reaction

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Winkler, Till; Groeger, Harald; Hummel, Werner; ChemCatChem; vol. 6; nb. 4; (2014); p. 961 - 964 View in Reaxys

O

O

HO

OH

H

Rx-ID: 38046168 View in Reaxys 11/94 Yield

Conditions & References With bis(norbornadiene)rhodium(l)tetrafluoroborate, (Sp)-2-[(R)-1-diphenylphosphinoethyl]-(Sp)-2η-diphenylphosphino-1,1η-biferrocene, hydrogen in methanol, Time= 20h, T= 20 °C , p= 37503.8Torr , Inert atmosphere, Autoclave Zirakzadeh, Afrooz; Gross, Manuela A.; Wang, Yaping; Mereiter, Kurt; Weissensteiner, Walter; Organometallics; vol. 33; nb. 8; (2014); p. 1945 - 1952 View in Reaxys

O

O

OH

H

Cl

Rx-ID: 36194105 View in Reaxys 12/94 Yield

Conditions & References Reaction Steps: 2 1: Geotrichum candidum CCT 1205 cells / water / 6 h / 30 °C / Microbiological reaction 2: sodium hypobromide; sodium hydroxide / water; 1,4-dioxane / 2 h / Cooling With sodium hypobromide, sodium hydroxide in 1,4-dioxane, water De Paula, Bruno R.S.; Zampieri, Davila S.; Rodrigues, J. Augusto R.; Moran, Paulo J.S.; Tetrahedron Asymmetry; vol. 24; nb. 17; (2013); p. 973 - 981 View in Reaxys Reaction Steps: 2 1: Saccharomyces cerevisiae CCT 3019 cells / 24 h / Microbiological reaction 2: sodium hypobromide; sodium hydroxide / water; 1,4-dioxane / 2 h / Cooling With sodium hypobromide, sodium hydroxide in 1,4-dioxane, water De Paula, Bruno R.S.; Zampieri, Davila S.; Rodrigues, J. Augusto R.; Moran, Paulo J.S.; Tetrahedron Asymmetry; vol. 24; nb. 17; (2013); p. 973 - 981 View in Reaxys Reaction Steps: 2 1: yeast type II from Saccharomyces cerevisiae / 16 h / Microbiological reaction 2: sodium hypobromide; sodium hydroxide / water; 1,4-dioxane / 2 h / Cooling With sodium hypobromide, sodium hydroxide in 1,4-dioxane, water De Paula, Bruno R.S.; Zampieri, Davila S.; Rodrigues, J. Augusto R.; Moran, Paulo J.S.; Tetrahedron Asymmetry; vol. 24; nb. 17; (2013); p. 973 - 981 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

O

OH

H

Br

Rx-ID: 36194113 View in Reaxys 13/94 Yield

Conditions & References Reaction Steps: 2 1: Geotrichum candidum CCT 1205 cells / water / 6 h / 30 °C / Microbiological reaction 2: sodium hypobromide; sodium hydroxide / water; 1,4-dioxane / 2 h / Cooling With sodium hypobromide, sodium hydroxide in 1,4-dioxane, water De Paula, Bruno R.S.; Zampieri, Davila S.; Rodrigues, J. Augusto R.; Moran, Paulo J.S.; Tetrahedron Asymmetry; vol. 24; nb. 17; (2013); p. 973 - 981 View in Reaxys Reaction Steps: 2 1: yeast type II from Saccharomyces cerevisiae / water / 8 h / 30 °C / Microbiological reaction 2: sodium hypobromide; sodium hydroxide / water; 1,4-dioxane / 2 h / Cooling With sodium hypobromide, sodium hydroxide in 1,4-dioxane, water De Paula, Bruno R.S.; Zampieri, Davila S.; Rodrigues, J. Augusto R.; Moran, Paulo J.S.; Tetrahedron Asymmetry; vol. 24; nb. 17; (2013); p. 973 - 981 View in Reaxys

O

OH

H

H O

Rx-ID: 36194139 View in Reaxys 14/94 Yield

Conditions & References Reaction Steps: 3 1: sulfuric acid / acetic acid / 16 h / 20 °C 2: yeast type II from Saccharomyces cerevisiae / water / 24 h / 30 °C / Microbiological reaction 3: sodium hypobromide; sodium hydroxide / water; 1,4-dioxane / 2 h / Cooling With sodium hypobromide, sulfuric acid, sodium hydroxide in 1,4-dioxane, water, acetic acid, 1: |Aldol Condensation De Paula, Bruno R.S.; Zampieri, Davila S.; Rodrigues, J. Augusto R.; Moran, Paulo J.S.; Tetrahedron Asymmetry; vol. 24; nb. 17; (2013); p. 973 - 981 View in Reaxys

O

O

OH

H

Rx-ID: 36194143 View in Reaxys 15/94 Yield

Conditions & References Reaction Steps: 2 1: yeast type II from Saccharomyces cerevisiae / water / 24 h / 30 °C / Microbiological reaction 2: sodium hypobromide; sodium hydroxide / water; 1,4-dioxane / 2 h / Cooling With sodium hypobromide, sodium hydroxide in 1,4-dioxane, water

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

De Paula, Bruno R.S.; Zampieri, Davila S.; Rodrigues, J. Augusto R.; Moran, Paulo J.S.; Tetrahedron Asymmetry; vol. 24; nb. 17; (2013); p. 973 - 981 View in Reaxys

OH

O

H

O

Rx-ID: 36194150 View in Reaxys 16/94 Yield

Conditions & References

61 %

10 : (R)- and (S)-3-Methylnonan-2-one (R)- and (S)-6g A solution of sodium hypobromite was prepared by dropwise addition of bromine (681 μL, 13.2 mmol) to a solution of sodium hydroxide (52 mmol) in water (20 mL) in an ice/salt bath. After all the bromine was consumed, the bright yellow solution was diluted with 1,4-dioxane (5 mL), and added dropwise to a cooled (cold water bath) solution of (R)-6a (95percent ee, 648 mg, 4 mmol) in dioxane (50 mL) and water (10 mL). The mixture was stirred for 2 h. Next, most of the dioxane/water mixture was evaporated under reduced pressure, the residue was diluted in water (40 mL), and extracted with CH2Cl2 (3 x 20 mL). The aqueous phase was acidified, and then extracted with CH2Cl2 (3 x 20 mL). The organic phase from the second extraction was dried over Na2SO4 and evaporated under reduced pressure to afford (R)-8a in 61percent yield, and 92percent ee as a colorless oil. [η]D 25

= -20.8 (c 0.87, CHCl3); lit.37 [η]D 25 = -22.7 (c 1.02, CHCl3) for the (R)-isomer. 1H NMR (CDCl3, 500 MHz) η 1.18 (d, 3H, J =

7.00 Hz), 2.67 (dd, 1H, J = 8.00, 13.5 Hz), 2.77 (sx, 1H, J = 7.00 Hz), 3.08 (dd, 1H, J = 6.50, 13.5 Hz), 7.17-7.31 (m, 5H);13C NMR (CDCl3, 125 MHz) η 16.5, 39.3, 41.2, 126.4, 128.4, 129.0, 139.0, 182.5.

With sodium hypobromide, sodium hydroxide in 1,4-dioxane, water, Time= 2h, Cooling De Paula, Bruno R.S.; Zampieri, Davila S.; Rodrigues, J. Augusto R.; Moran, Paulo J.S.; Tetrahedron Asymmetry; vol. 24; nb. 17; (2013); p. 973 - 981 View in Reaxys O

O

O

OH O

O

O

O

H

H

HO

O

H

H

Rx-ID: 36848163 View in Reaxys 17/94 Yield

Conditions & References General procedure for the hydrolase-catalysed kinetic resolution of the 3-aryl alkanoic ethyl esters 2a–c (analytical scale) General procedure: A spatula tip of enzyme (η5–10mg, amount not critical) was added to the ester substrate 2a–c (η50mg) in a 0.1M phosphate buffer, pH 7 (4.5mL). The small test tubes were sealed and agitated at 700–750rpm and incubated for the appropriate length of time and temperature. The aqueous layer was extracted with diethyl ether (3×5mL) and the combined organic extracts were filtered through Celite® and concentrated under reduced pressure. The sample was analysed by 1H NMR spectroscopy, reconcentrated and dissolved in a mixture of isopropanol/hexane [10:90 (HPLC grade)]. The enantioselectivity was determined by chiral HPLC. The results of the screens are summarised in Tables 1 and 3.

With Pseudomonas stutzeri hydrolase in aq. phosphate buffer, Time= 72h, T= 20 °C , pH= 7, Resolution of racemate, Enzymatic reaction, Reagent/catalyst, enantioselective reaction

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Deasy, Rebecca E.; Moody, Thomas S.; Maguire, Anita R.; Tetrahedron Asymmetry; vol. 24; nb. 23; (2013); p. 1480 - 1487 View in Reaxys

OH

O

O

HO

O

H

O

H

Rx-ID: 36848168 View in Reaxys 18/94 Yield

Conditions & References Reaction Steps: 2 1: sulfuric acid / Reflux 2: Pseudomonas stutzeri hydrolase / aq. phosphate buffer / 72 h / 20 °C / pH 7 / Resolution of racemate; Enzymatic reaction With sulfuric acid, Pseudomonas stutzeri hydrolase in aq. phosphate buffer Deasy, Rebecca E.; Moody, Thomas S.; Maguire, Anita R.; Tetrahedron Asymmetry; vol. 24; nb. 23; (2013); p. 1480 - 1487 View in Reaxys

O

OH

O

H N OH

Rx-ID: 33275296 View in Reaxys 19/94 Yield

Conditions & References

98 %

With sulfuric acid in 1,4-dioxane, water, Time= 5.3h, T= 115 °C , Inert atmosphere, optical yield given as percent ee Morales, Marvin R.; Mellem, Kevin T.; Myers, Andrew G.; Angewandte Chemie - International Edition; vol. 51; nb. 19; (2012); p. 4568 - 4571 View in Reaxys

N O

O O

OH

N

H

O Pol (v1)

Rx-ID: 36225458 View in Reaxys 20/94

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Yield

Conditions & References Preparation of (R)-2-Methyl-3-phenylpropanoic acid (10).

Using NaOH/dioxane: Resin 9 (0.38 g, 0.33 mmol) was swollen in excess NaOH 2 N (15 mL): dioxane (15 mL). After 4 h at 100 °C, the deacylated resin was filtered off and the filtrate was acidified to pH 2 with HCl and extracted with ethyl acetate. The crude product was purified by flash column chromatography to yield compound 10 as colorless oil. Yield 30percent (4 steps based on the original loading of Wang resin); Rf = 0.63 (n-hexane:EA = 1:1); 1H NMR (300 MHz, CDCl3) η 7.40-7.00 (5H, m), 3.10 (1H, dd, J = 7, 13 Hz), 2.75 (1H, m), 2.67 (1H, dd, J = 7, 13 Hz), 1.16 (3H, d, J = 7Hz); the enantiomer excess (ee) was determined by HPLC to be > 99percent after conversion acid to ester with CH2N2.

With sodium hydroxide in 1,4-dioxane Solid phase= Wang resin, Time= 4h, T= 100 °C Nguyen, Quynh Pham Bao; Kim, Taek Hyeon; Bulletin of the Korean Chemical Society; vol. 33; nb. 12; (2012); p. 4223 4226 View in Reaxys

O N

O

O N

OH

N

O

HN

H NH N

O

O

N

N O

Rx-ID: 32574411 View in Reaxys 21/94 Yield 78 %

Conditions & References Stage 1: With sodium hydroxide in 1,4-dioxane, water, T= 100 °C Stage 2: With hydrogenchloride in 1,4-dioxane, water, pH= Ca. 2, optical yield given as percent ee Jeong, Song Yi; Nguyen, Quynh Pham Bao; Kim, Hyung Jin; Kim, Taek Hyeon; Bulletin of the Korean Chemical Society; vol. 32; nb. 11; (2011); p. 4133 - 4136 View in Reaxys

O

O O

O

N

N

O O

OH

OH

H

O

Rx-ID: 29454099 View in Reaxys 22/94 Yield

Conditions & References With Candida antarctica lipase A Phe149Tyr/Ile150Asn/Phe233Gly in acetonitrile, Time= 0.25h, T= 20 °C , aq. phosphate buffer, aq. buffer, Enzymatic reaction, optical yield given as percent ee, enantioselective reaction Engstroem, Karin; Nyhlen, Jonas; Sandstroem, Anders G.; Baeckvall, Jan-E.; Journal of the American Chemical Society; vol. 132; nb. 20; (2010); p. 7038 - 7042 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

O O

O

N

O N

O O

OH

OH

H

O

HO

H

Rx-ID: 29454100 View in Reaxys 23/94 Yield

Conditions & References With Candida antarctica lipase A wild type in acetonitrile, Time= 4h, T= 20 °C , aq. phosphate buffer, aq. buffer, Enzymatic reaction, optical yield given as percent ee, enantioselective reaction Engstroem, Karin; Nyhlen, Jonas; Sandstroem, Anders G.; Baeckvall, Jan-E.; Journal of the American Chemical Society; vol. 132; nb. 20; (2010); p. 7038 - 7042 View in Reaxys With Candida antarctica lipase A Phe233Gly in acetonitrile, Time= 0.1h, T= 20 °C , aq. phosphate buffer, aq. buffer, Enzymatic reaction, optical yield given as percent ee, enantioselective reaction Engstroem, Karin; Nyhlen, Jonas; Sandstroem, Anders G.; Baeckvall, Jan-E.; Journal of the American Chemical Society; vol. 132; nb. 20; (2010); p. 7038 - 7042 View in Reaxys

N (v1)

Pol

O

N O

OH

O O

N (v1)

Pol

H

HN O O

Rx-ID: 28766708 View in Reaxys 24/94 Yield

Conditions & References With sodium hydroxide in 1,4-dioxane, Time= 4h Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron Letters; vol. 50; nb. 28; (2009); p. 4015 - 4018 View in Reaxys

O

O

O

OH

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

O

O

O

OH

H

O

O

HO

H

Rx-ID: 28960998 View in Reaxys 25/94 Yield

Conditions & References With 2-phenyl-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyrimidine, N-ethyl-N,N-diisopropylamine in toluene, Time= 24h, T= 0 °C , optical yield given as percent ee, enantioselective reaction Yang, Xing; Birman, Vladimir B.; Advanced Synthesis and Catalysis; vol. 351; nb. 14-15; (2009); p. 2301 - 2304 View in Reaxys

O O

O OH

O

O

HN

H

HO

H

Rx-ID: 29317075 View in Reaxys 26/94 Yield

Conditions & References With bis(norbornadiene)rhodium(l)tetrafluoroborate, (S(p),S(p))-2,2''-bis[bis(3,5-dimethylphenyl)phosphino]-1,1''-biferrocene, hydrogen in methanol, Time= 15h, T= 25 °C , p= 3750.38Torr , Autoclave, optical yield given as percent ee Espino, Gustavo; Xiao, Li; Puchberger, Michael; Mereiter, Kurt; Spindler, Felix; Manzano, Blanca R.; Jalon, Felix A.; Weissensteiner, Walter; Dalton Transactions; nb. 15; (2009); p. 2751 - 2763 View in Reaxys

OH

O

Br

O

O NH O O

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O O

OH

O

O N

H

HO

Rx-ID: 26018125 View in Reaxys 27/94 Yield

Conditions & References Multistep reaction.

Green, Rachel; Merritt, Andrew T.; Bull, Steven D.; Chemical Communications; vol. 8; nb. 4; (2008); p. 508 - 510 View in Reaxys

O

O OH

O

O

N H

Rx-ID: 10462650 View in Reaxys 28/94 Yield 77 %

Conditions & References With lithium hydroxide in tetrahydrofuran, T= 0 - 20 °C Suzuki, Takayoshi; Hisakawa, Shinya; Itoh, Yukihiro; Maruyama, Sakiko; Kurotaki, Mineko; Nakagawa, Hidehiko; Miyata, Naoki; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 6; (2007); p. 1558 - 1561 View in Reaxys

O

O

OH

OH

H

H 2N

Rx-ID: 10652662 View in Reaxys 29/94 Yield

Conditions & References 12.i :(η)-2-Methy-3-phenylpropionic acid ter/-butylamine salt, reaction time 40 minutes, conversion 100percent. The free acid was liberated by partitioning between dichloromethane and 2M HCl. The organic layer was dried (Na2SO4), filtered and the solvent was evaporated, then the product was distilled (kugelrohr, 150 0C, 0.5 mbar) to give (η)-2-Methy-3- phenylpropionic acid as a colorless liquid, [η] I 1 DI -22.1, c = 1.02, CHCl3. Lit. (E. Tyrell,M.W.H. Tang, G.A. Skinner and J. Fawcett, Tetrahedron, 1996, 52, 9841-9852, [η] I 2 ^00 -23.1 c = l, CHCI3). ee 85percent (derivatised using TMS-diazomethane, Chirasil Dex CB column, 25m x 0.25 mm, injector/detector 200 0C, helium 20 psi, 100 0C for 21 minutes then ramp at 15 °C/min to 200 0C, hold for 5 minutes, retention times R 30.40 minutes, S 31.06 minutes, (E)-methyl 2-methylcinnamate, 34.79 minutes). 1H NMR analysis of the (S)<n="32"/>methyl mandelate (E. Tyrell, M.W.H. Tang, G.A. Skinner and J. Fawcett, Tetrahedron, 1996, 52, 9841 -9852) confirmed assignment of (^-configuration.

With hydrogenchloride in dichloromethane, water Patent; DOW GLOBAL TECHNOLOGIES INC.; WO2007/123957; (2007); (A2) English View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

N

O

O

N

O

N

H

NH

O

OH

Rx-ID: 11198115 View in Reaxys 30/94 Yield

Conditions & References With sodium hydroxide in 1,4-dioxane, Time= 1h, Heating Le, Thanh Nguyen; Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron Letters; vol. 48; nb. 44; (2007); p. 7834 - 7837 View in Reaxys

O N

OH

O N

O

H

N O

NH

Rx-ID: 11198117 View in Reaxys 31/94 Yield

Conditions & References With sodium hydroxide in 1,4-dioxane, Time= 1h, Heating Le, Thanh Nguyen; Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron Letters; vol. 48; nb. 44; (2007); p. 7834 - 7837 View in Reaxys

O

O

OH

H

N

O

O

Rx-ID: 11785689 View in Reaxys 32/94 Yield

Conditions & References Reaction Steps: 2 1.1: LDA / tetrahydrofuran / -78 °C 1.2: 63 percent / tetrahydrofuran / -78 - 20 °C 2.1: 77 percent / aq. LiOH / tetrahydrofuran / 0 - 20 °C With lithium hydroxide, lithium diisopropyl amide in tetrahydrofuran

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Suzuki, Takayoshi; Hisakawa, Shinya; Itoh, Yukihiro; Maruyama, Sakiko; Kurotaki, Mineko; Nakagawa, Hidehiko; Miyata, Naoki; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 6; (2007); p. 1558 - 1561 View in Reaxys

OH

O

O

H

Cl

Rx-ID: 11786208 View in Reaxys 33/94 Yield

Conditions & References Reaction Steps: 3 1.1: nBuLi / tetrahydrofuran / -78 °C 1.2: 83 percent / tetrahydrofuran / -78 °C 2.1: LDA / tetrahydrofuran / -78 °C 2.2: 63 percent / tetrahydrofuran / -78 - 20 °C 3.1: 77 percent / aq. LiOH / tetrahydrofuran / 0 - 20 °C With lithium hydroxide, n-butyllithium, lithium diisopropyl amide in tetrahydrofuran Suzuki, Takayoshi; Hisakawa, Shinya; Itoh, Yukihiro; Maruyama, Sakiko; Kurotaki, Mineko; Nakagawa, Hidehiko; Miyata, Naoki; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 6; (2007); p. 1558 - 1561 View in Reaxys Reaction Steps: 4 1: 82 percent / Et3N / tetrahydrofuran / 1 h / 0 °C 2: 83 percent / Mg / diethyl ether / reflux, 4 h -> ambient temperature 3: LDA / tetrahydrofuran / -100 deg C, 2 h -> -50 deg C 4: 3 M aq. HCl / dioxane / 42 h / 90 - 95 °C With hydrogenchloride, magnesium, triethylamine, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane, diethyl ether Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

O

O

HO

OH

H

Rx-ID: 3962087 View in Reaxys 34/94 Yield 61 % Spectr.

Conditions & References With hydrogen, (S,R)-<(P-N)RhNBD>ClO4 in ethanol, Time= 3.5h, T= 30 °C , study of the asymmetric hydrogenation of various prochiral substrates with chiral ligands containing rhodium(I) complexes of ferrocenylphosphonium as asymmetric catalysts, Product distribution Appelton, Trevor D.; Cullen, William R.; Evans, Sthephen; Kim, Tae-Jeong; Trotter, James; Journal of Organometallic Chemistry; vol. 279; (1985); p. 5 - 22 View in Reaxys

41 %Chromat.

D20 With hydrogen, 1-(1-dimethylaminoethyl)-2-isopropylthio-3-diphenylphosphino-ferrocene, bis(bicyclo[2.2.1]hepta-2,5-diene)rhodium(I) tetrafluoroborate in methanol, Time= 21h, T= 25 °C , p= 750.075Torr , Product distribution / selectivity Patent; SOLVIAS AG; WO2006/117369; (2006); (A1) German View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

N

OH O

O

OH

O Cl NH

H

H

H

HO

OH

Rx-ID: 10467878 View in Reaxys 35/94 Yield

Conditions & References With hydrogenchloride in 1,4-dioxane Andersson, Fredrik; Hedenstroem, Erik; Tetrahedron Asymmetry; vol. 17; nb. 13; (2006); p. 1952 - 1957 View in Reaxys

O

O

O

O

N

OH

O HN

O

H

Rx-ID: 11137427 View in Reaxys 36/94 Yield 12 mg, 100 %

Conditions & References With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, Time= 16h, T= 0 - 20 °C Davies, Stephen G.; Garner, A. Christopher; Roberts, Paul M.; Smith, Andrew D.; Sweet, Miles J.; Thomson, James E.; Organic and Biomolecular Chemistry; vol. 4; nb. 14; (2006); p. 2753 - 2768 View in Reaxys

O

Br

(1R,2R)-O-Merrifield bound N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-2'-phenylacetamide

OH

H

Rx-ID: 11423706 View in Reaxys 37/94 Yield

Conditions & References Reaction Steps: 2 1.1: KHMDS / tetrahydrofuran; toluene / 1 h / -78 °C 1.2: 78 percent / 5 h / -40 °C 2.1: 100 percent / aq. H2O2; LiOH / tetrahydrofuran / 16 h / 0 - 20 °C With lithium hydroxide, dihydrogen peroxide, potassium hexamethylsilazane in tetrahydrofuran, toluene Davies, Stephen G.; Garner, A. Christopher; Roberts, Paul M.; Smith, Andrew D.; Sweet, Miles J.; Thomson, James E.; Organic and Biomolecular Chemistry; vol. 4; nb. 14; (2006); p. 2753 - 2768 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

OH

HO

H Br

O

Rx-ID: 9883488 View in Reaxys 38/94 Yield 16.6 mg

Conditions & References Multistep reaction Kotake, Tomoya; Hayashi, Yoshio; Rajesh; Mukai, Yoshie; Takiguchi, Yuka; Kimura, Tooru; Kiso, Yoshiaki; Tetrahedron; vol. 61; nb. 15; (2005); p. 3819 - 3833 View in Reaxys

O

OH

O

O I

H

HO

HO

H

Rx-ID: 9901344 View in Reaxys 39/94 Yield

Conditions & References Multistep reaction. Title compound not separated from byproducts Kotake, Tomoya; Hayashi, Yoshio; Rajesh; Mukai, Yoshie; Takiguchi, Yuka; Kimura, Tooru; Kiso, Yoshiaki; Tetrahedron; vol. 61; nb. 15; (2005); p. 3819 - 3833 View in Reaxys

O

N

OH

O

O

O O

H

N Br

O

O

Rx-ID: 9658934 View in Reaxys 40/94 Yield

Conditions & References Stage 1: With lithium diisopropyl amide in tetrahydrofuran, T= -78 - 0 °C Stage 2: With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, T= 0 °C , Further stages.

Kotake, Tomoya; Rajesh; Hayashi, Yoshio; Mukai, Yoshie; Ueda, Mitsuhiro; Kimura, Tooru; Kiso, Yoshiaki; Tetrahedron Letters; vol. 45; nb. 18; (2004); p. 3651 - 3654 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

O

I

N N O O O

O

OH

O

O H

HO

H

Rx-ID: 9685552 View in Reaxys 41/94 Yield

Conditions & References Stage 1: With lithium diisopropyl amide in tetrahydrofuran, T= -78 - 0 °C Stage 2: With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, T= 0 °C , Further stages. Title compound not separated from byproducts.

Kotake, Tomoya; Rajesh; Hayashi, Yoshio; Mukai, Yoshie; Ueda, Mitsuhiro; Kimura, Tooru; Kiso, Yoshiaki; Tetrahedron Letters; vol. 45; nb. 18; (2004); p. 3651 - 3654 View in Reaxys

O

O

O

OH

O HO

HO

H

HO

H

Rx-ID: 10036551 View in Reaxys 42/94 Yield

Conditions & References With phosphate buffer, 2-bromohexanoic acid, Nocardia diaphanozonaria JCM 3208 whole cells in water, T= 30 °C , pH= 7.0, Title compound not separated from byproducts Kato, Dai-Ichiro; Miyamoto, Kenji; Ohta, Hiromichi; Tetrahedron Asymmetry; vol. 15; nb. 18; (2004); p. 2965 - 2973 View in Reaxys

O

OH

O H

O O

HO

H

N HO

Rx-ID: 9618144 View in Reaxys 43/94 Yield

Conditions & References With hydrogenchloride, acetic acid, Heating, Title compound not separated from byproducts

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Srivastava, Stuti; Goswami, Lalit N.; Dikshit, Dinesh K.; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 42; nb. 10; (2003); p. 2628 - 2631 View in Reaxys

OH

O N

H N

O

O

Rx-ID: 9043914 View in Reaxys 44/94 Yield

Conditions & References

96 %

With sodium hydroxide in 1,4-dioxane, Time= 0.5h, Heating Lee, Gue-Jae; Kim, Taek Hyeon; Kim, Jae Nyoung; Lee, Uk; Tetrahedron Asymmetry; vol. 13; nb. 1; (2002); p. 9 - 12 View in Reaxys

O

OH

O O

N

H O

Rx-ID: 8837301 View in Reaxys 45/94 Yield 60 %

Conditions & References With lithium hydroxide in tetrahydrofuran, Time= 25h, T= 0 - 24 °C Alexander; Cook; Gibson; Kennedy; Journal of the Chemical Society. Perkin Transactions 1; nb. 13; (2001); p. 1538 - 1549 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

OH

O O O

O

N

H O

HO

H

Rx-ID: 8848295 View in Reaxys 46/94 Yield

Conditions & References With lithium hydroxide in tetrahydrofuran, Time= 25h, T= 0 - 24 °C , Title compound not separated from byproducts.

Alexander; Cook; Gibson; Kennedy; Journal of the Chemical Society. Perkin Transactions 1; nb. 13; (2001); p. 1538 - 1549 View in Reaxys

OH

O

O

O O

H

N

HO

H

O

Rx-ID: 8849963 View in Reaxys 47/94 Yield

Conditions & References With lithium hydroxide in tetrahydrofuran, Time= 25h, T= 0 - 24 °C , Title compound not separated from byproducts.

Alexander; Cook; Gibson; Kennedy; Journal of the Chemical Society. Perkin Transactions 1; nb. 13; (2001); p. 1538 - 1549 View in Reaxys

O

OH

O O O

H

N

HO

H

O

Rx-ID: 8852653 View in Reaxys 48/94

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Yield

Conditions & References With lithium hydroxide in tetrahydrofuran, Time= 25h, T= 0 - 24 °C , Title compound not separated from byproducts Alexander; Cook; Gibson; Kennedy; Journal of the Chemical Society. Perkin Transactions 1; nb. 13; (2001); p. 1538 - 1549 View in Reaxys

O

OH

HO

H O

Rx-ID: 8912508 View in Reaxys 49/94 Yield 95 %

Conditions & References With ammonium cerium(IV) nitrate in water, acetonitrile, Time= 1h, T= 0 °C Palomo, Claudio; Oiarbide, Mikel; Mielgo, Antonia; Gonzalez, Alberto; Garcia, Jesus M.; Landa, Cristina; Lecumberri, Ainara; Linden, Anthony; Organic Letters; vol. 3; nb. 21; (2001); p. 3249 - 3252 View in Reaxys

O

polymer-bound NMe3 (1+)*SCN(1-)

OH

H

Br

Rx-ID: 15262192 View in Reaxys 50/94 Yield

Conditions & References Reaction Steps: 2 1.1: KN(SiMe3)2 / tetrahydrofuran; toluene / 4 h / -78 °C 1.2: 80 percent / tetrahydrofuran; toluene / -78 - 50 °C 2.1: 95 percent / CAN / acetonitrile; H2O / 1 h / 0 °C With ammonium cerium(IV) nitrate, potassium hexamethylsilazane in tetrahydrofuran, water, toluene, acetonitrile Palomo, Claudio; Oiarbide, Mikel; Mielgo, Antonia; Gonzalez, Alberto; Garcia, Jesus M.; Landa, Cristina; Lecumberri, Ainara; Linden, Anthony; Organic Letters; vol. 3; nb. 21; (2001); p. 3249 - 3252 View in Reaxys

O

OH

OH N

H

O

Rx-ID: 4016112 View in Reaxys 51/94 Yield 95 %

Conditions & References With sulfuric acid in 1,4-dioxane, Time= 6h, Heating Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; McKinstry, Lydia; Kopecky, David J.; Gleason, James L.; Journal of the American Chemical Society; vol. 119; nb. 28; (1997); p. 6496 - 6511 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

87 %

With sulfuric acid in 1,4-dioxane, Heating Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; Gleason, James L.; Journal of the American Chemical Society; vol. 116; nb. 20; (1994); p. 9361 - 9362 View in Reaxys

83 %

With sulfuric acid in 1,4-dioxane, Time= 1h, Heating Bach, Jordi; Galobardes, Marta; Garcia, Jordi; Romea, Pedro; Cristina, Tey; Urpi, Felix; Vilarrasa, Jaume; Tetrahedron Letters; vol. 39; nb. 37; (1998); p. 6765 - 6768 View in Reaxys Reaction Steps: 2 1: lithium aluminium tetrahydride; ethyl acetate / hexane; tetrahydrofuran / 1.08 h / -78 - 0 °C / Neutral conditions 2: 2-methyl-but-2-ene; sodium chlorite; sodium dihydrogen phosphate monohydrate / tetrahydrofuran; tert-butyl alcohol; water / 0.83 h / 23 °C With sodium chlorite, lithium aluminium tetrahydride, sodium dihydrogen phosphate monohydrate, 2-methyl-but-2-ene, ethyl acetate in tetrahydrofuran, hexane, water, tert-butyl alcohol Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; Smith, William J.; Roush, William R.; Organic Syntheses; vol. 77; (2000); p. 29 - 29 View in Reaxys

O

OH

O

O H

O HN

HO

H

O

Rx-ID: 8649941 View in Reaxys 52/94 Yield

Conditions & References With methanol, potassium hydroxide, Heating, Hydrolysis, Title compound not separated from byproducts Chandrasekhar, Sosale; Kausar, Amina; Tetrahedron Asymmetry; vol. 11; nb. 11; (2000); p. 2249 - 2253 View in Reaxys

O

OH

H O N

Rx-ID: 15735867 View in Reaxys 53/94 Yield

Conditions & References Reaction Steps: 3 1.1: LDA / tetrahydrofuran / -78 °C 1.2: 95 percent / tetrahydrofuran 2.1: 24 h / Heating 3.1: KOH; MeOH / Heating With methanol, potassium hydroxide, lithium diisopropyl amide in tetrahydrofuran, 1.1: Metallation / 1.2: Alkylation / 2.1: Ring cleavage / 3.1: Hydrolysis Chandrasekhar, Sosale; Kausar, Amina; Tetrahedron Asymmetry; vol. 11; nb. 11; (2000); p. 2249 - 2253 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

OH

H

O N

Rx-ID: 15740935 View in Reaxys 54/94 Yield

Conditions & References Reaction Steps: 2 1: 24 h / Heating 2: KOH; MeOH / Heating With methanol, potassium hydroxide, 1: Ring cleavage / 2: Hydrolysis Chandrasekhar, Sosale; Kausar, Amina; Tetrahedron Asymmetry; vol. 11; nb. 11; (2000); p. 2249 - 2253 View in Reaxys

OH

O O

H H

Rx-ID: 46173360 View in Reaxys 55/94 Yield

Conditions & References With sodium chlorite, sodium dihydrogen phosphate monohydrate, 2-methyl-but-2-ene in tetrahydrofuran, water, tert-butyl alcohol, Time= 0.833333h, T= 23 °C Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; Smith, William J.; Roush, William R.; Organic Syntheses; vol. 77; (2000); p. 29 - 29 View in Reaxys

O

OH

O O

O

N

H O

HO

H

O HN

O

Rx-ID: 5041597 View in Reaxys 56/94 Yield 94 %

Conditions & References With lithium hydroxide, Yield given Gibson, Colin L.; Gillon, Karen; Cook, Stuart; Tetrahedron Letters; vol. 39; nb. 37; (1998); p. 6733 - 6736 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

OH

O O

O

N

H O

HO

H

O HN

O

Rx-ID: 5041598 View in Reaxys 57/94 Yield

Conditions & References

95 %

With lithium hydroxide, Yield given Gibson, Colin L.; Gillon, Karen; Cook, Stuart; Tetrahedron Letters; vol. 39; nb. 37; (1998); p. 6733 - 6736 View in Reaxys

O

OH

O O

N

H O

O HN

O

Rx-ID: 5114767 View in Reaxys 58/94 Yield 79 %, 79 %

Conditions & References With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, water, Time= 1.5h, T= 0 °C Hintermann, Tobias; Seebach, Dieter; Helvetica Chimica Acta; vol. 81; nb. 11; (1998); p. 2093 - 2126 View in Reaxys

O

Br

potassium-compound of propionic acid-<1-methyl-2-oxo-propylidenehydrazide>

OH

H

Rx-ID: 16745184 View in Reaxys 59/94 Yield

Conditions & References Reaction Steps: 2 1: 82 percent / LDA, LiCl / tetrahydrofuran / 0.75 h / 0 °C 2: 83 percent / H2SO4 / dioxane / 1 h / Heating With sulfuric acid, lithium chloride, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane Bach, Jordi; Galobardes, Marta; Garcia, Jordi; Romea, Pedro; Cristina, Tey; Urpi, Felix; Vilarrasa, Jaume; Tetrahedron Letters; vol. 39; nb. 37; (1998); p. 6765 - 6768 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Reaction Steps: 2 1: 90 percent / NaHMDS 2: LiOH, H2O2 With lithium hydroxide, dihydrogen peroxide, sodium hexamethyldisilazane Simpson, Thomas J.; Smith, Robert W.; Westaway, Susan M.; Willis, Christine L.; Buss, Antony D.; Cannell, Richard J. P.; Dawson, Michael J.; Rudd, Brian A. M.; Tetrahedron Letters; vol. 38; nb. 30; (1997); p. 5367 - 5370 View in Reaxys Reaction Steps: 2 1: 90 percent / LiCl, diisopropylamine, n-BuLi / tetrahydrofuran; hexane / 0.25 h / 0 °C 2: 95 percent / 9 N aq. H2SO4 / dioxane / 6 h / Heating With n-butyllithium, sulfuric acid, diisopropylamine, lithium chloride in tetrahydrofuran, 1,4-dioxane, hexane Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; McKinstry, Lydia; Kopecky, David J.; Gleason, James L.; Journal of the American Chemical Society; vol. 119; nb. 28; (1997); p. 6496 - 6511 View in Reaxys

O

OH

OH

O N

H

HO

H

O

Rx-ID: 4016116 View in Reaxys 60/94 Yield

Conditions & References With tetra(n-butyl)ammonium hydroxide in water, tert-butyl alcohol, Heating, Title compound not separated from byproducts Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; Gleason, James L.; Journal of the American Chemical Society; vol. 116; nb. 20; (1994); p. 9361 - 9362 View in Reaxys With tetra(n-butyl)ammonium hydroxide in tert-butyl alcohol, Heating, Yield given. Yields of byproduct given. Title compound not separated from byproducts Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; McKinstry, Lydia; Kopecky, David J.; Gleason, James L.; Journal of the American Chemical Society; vol. 119; nb. 28; (1997); p. 6496 - 6511 View in Reaxys

O

OH

H

O

N

O

O

Rx-ID: 4833359 View in Reaxys 61/94 Yield

Conditions & References With lithium hydroxide, dihydrogen peroxide Simpson, Thomas J.; Smith, Robert W.; Westaway, Susan M.; Willis, Christine L.; Buss, Antony D.; Cannell, Richard J. P.; Dawson, Michael J.; Rudd, Brian A. M.; Tetrahedron Letters; vol. 38; nb. 30; (1997); p. 5367 - 5370 View in Reaxys Reaction Steps: 2 1: 93 percent / PhCH2OH / tetrahydrofuran / 1 h / 0 °C 2: hydrogen

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

With hydrogen, benzyl alcohol in tetrahydrofuran Evans, D. A.; Ennis, M. D.; Mathre, D. J.; Journal of the American Chemical Society; vol. 104; nb. 6; (1982); p. 1737 - 1739 View in Reaxys

O

H

N

HO

H

O

OH

H

Rx-ID: 17169383 View in Reaxys 62/94 Yield

Conditions & References Reaction Steps: 2 1: 95 percent / LiCl, diisopropylamine, n-BuLi / tetrahydrofuran; hexane / -78 °C 2: aq. n-Bu4NOH / 2-methyl-propan-2-ol / Heating With n-butyllithium, tetra(n-butyl)ammonium hydroxide, diisopropylamine, lithium chloride in tetrahydrofuran, hexane, tert-butyl alcohol Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; McKinstry, Lydia; Kopecky, David J.; Gleason, James L.; Journal of the American Chemical Society; vol. 119; nb. 28; (1997); p. 6496 - 6511 View in Reaxys Reaction Steps: 2 1: 1.) LDA, LiCl / 1.) THF, from -78 to 23 deg C, 80 min, 2.) THF, -78 deg C, 8 h 2: tetra-n-butylammonium hydroxide / H2O; 2-methyl-propan-2-ol / Heating With tetra(n-butyl)ammonium hydroxide, lithium chloride, lithium diisopropyl amide in water, tert-butyl alcohol Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; Gleason, James L.; Journal of the American Chemical Society; vol. 116; nb. 20; (1994); p. 9361 - 9362 View in Reaxys

O

OH

O

1.2.2.3-tetramethyl-cyclopentylcarbinol

H

Cl

Rx-ID: 17172142 View in Reaxys 63/94 Yield

Conditions & References Reaction Steps: 3 1: 83 percent / Et3N / tetrahydrofuran / 0.17 h 2: 95 percent / LiCl, diisopropylamine, n-BuLi / tetrahydrofuran; hexane / -78 °C 3: aq. n-Bu4NOH / 2-methyl-propan-2-ol / Heating With n-butyllithium, tetra(n-butyl)ammonium hydroxide, triethylamine, diisopropylamine, lithium chloride in tetrahydrofuran, hexane, tert-butyl alcohol Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; McKinstry, Lydia; Kopecky, David J.; Gleason, James L.; Journal of the American Chemical Society; vol. 119; nb. 28; (1997); p. 6496 - 6511 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

OH

O

O O

HN

H

N

O O

O

Rx-ID: 4368729 View in Reaxys 64/94 Yield

Conditions & References

95 %, 100 %

With lithium hydroperoxide in tetrahydrofuran, T= 0 °C Sudo; Saigo; Tetrahedron Asymmetry; vol. 6; nb. 9; (1995); p. 2153 - 2156 View in Reaxys

95 %, 100 %

With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, Time= 2.5h, T= 0 °C Sudo, Atsushi; Saigo, Kazuhiko; Tetrahedron Asymmetry; vol. 7; nb. 10; (1996); p. 2939 - 2956 View in Reaxys

O

OH

O

H N O O

Rx-ID: 4493212 View in Reaxys 65/94 Yield

Conditions & References

78 %

With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, Time= 1h, T= 0 °C Tyrrell, Elizabeth; Tsang, Michael W. H.; Skinner, George A.; Fawcett, John; Tetrahedron; vol. 52; nb. 29; (1996); p. 9841 9852 View in Reaxys

O

OH

O H

O

HO

H

N

O

Rx-ID: 4289289 View in Reaxys 66/94 Yield

Conditions & References With sulfuric acid in acetic acid, Time= 4h, Heating, Yield given. Yields of byproduct given. Title compound not separated from byproducts Kanemasa; Ueno; Onimura; Kikukawa; Yamamoto; Tetrahedron; vol. 51; nb. 38; (1995); p. 10453 - 10462 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

HO

O Br

N

O

O

OH

O O H

NH HO

H

Rx-ID: 2400803 View in Reaxys 67/94 Yield

Conditions & References With lithium hydroxide, lithium diisopropyl amide, 1.) THF, 0 deg C, Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Davies; Doisneau; Prodger; Sanganee; Tetrahedron Letters; vol. 35; nb. 15; (1994); p. 2373 - 2376 View in Reaxys

O

O

O

OH

H

N

O

Rx-ID: 2515342 View in Reaxys 68/94 Yield 63 %

Conditions & References With lithium hydroxide, dihydrogen peroxide in tetrahydrofuran, water, Time= 120h, Ambient temperature Tanner; Birgersson; Gogoll; Luthman; Tetrahedron; vol. 50; nb. 32; (1994); p. 9797 - 9824 View in Reaxys

O

Br

C O

OH

H

Rx-ID: 18188314 View in Reaxys 69/94 Yield

Conditions & References Reaction Steps: 2 1: 1.) LDA, LiCl / 1.) THF, from -78 to 23 deg C, 80 min, 2.) THF, 0 deg C, 0.2 h 2: 87 percent / 18 N H2SO4 / dioxane / Heating With sulfuric acid, lithium chloride, lithium diisopropyl amide in 1,4-dioxane

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Myers, Andrew G.; Yang, Bryant H.; Chen, Hou; Gleason, James L.; Journal of the American Chemical Society; vol. 116; nb. 20; (1994); p. 9361 - 9362 View in Reaxys

O

O O

OH

O

N

N

O

OH

H

O

O

Rx-ID: 3108371 View in Reaxys 70/94 Yield

Conditions & References With phosphate buffer, water in acetonitrile, T= 25 °C , η-chymotrypsin as catalyst, pH: 7.5; stereospecifity in hydrolysis of acylated η-chymotrypsins, Rate constant, Mechanism Oetvoes, Laszlo; Kraicsovits, Ferenc; Tetrahedron; vol. 48; nb. 23; (1992); p. 5009 - 5014 View in Reaxys

O

O O

O

Br

OH

O

O

O

O

O

O

O

O

OH

OH

Br

O Br

O

O

O

O

O

O O O

O

H

O

O OH

O Br

O OH

Rx-ID: 3243144 View in Reaxys 71/94 Yield

Conditions & References Yield given. Multistep reaction. Yields of byproduct given Wilson; Burk; Biftu; Ball; Hoogsteen; Journal of Organic Chemistry; vol. 57; nb. 26; (1992); p. 7151 - 7158 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O O

OH

O

O O O

O O

OH

O

O

HO

O

H

O O

Rx-ID: 19576306 View in Reaxys 72/94 Yield

Conditions & References Reaction Steps: 4 1: 68 percent / 0.2percent K2CO3 / methanol / 1.33 h / 30 °C 2: 89 percent / 4-(N,N-dimethylamino)pyridine / pyridine-d5 / 0.05 h / 80 °C 3: 89 percent / 3percent methanolic HCl / 16 h / Ambient temperature With hydrogenchloride, dmap, potassium carbonate in methanol, perdeuteriopyridine Wilson; Burk; Biftu; Ball; Hoogsteen; Journal of Organic Chemistry; vol. 57; nb. 26; (1992); p. 7151 - 7158 View in Reaxys

O HO

O OH OH O

O O O

HO

O

OH

O

OH

H O O

Rx-ID: 19576313 View in Reaxys 73/94 Yield

Conditions & References Reaction Steps: 5 1: 73 percent / ethyl acetate; diethyl ether / 0.08 h / -15 °C 2: 68 percent / 0.2percent K2CO3 / methanol / 1.33 h / 30 °C 3: 89 percent / 4-(N,N-dimethylamino)pyridine / pyridine-d5 / 0.05 h / 80 °C 4: 89 percent / 3percent methanolic HCl / 16 h / Ambient temperature With hydrogenchloride, dmap, potassium carbonate in methanol, perdeuteriopyridine, diethyl ether, ethyl acetate Wilson; Burk; Biftu; Ball; Hoogsteen; Journal of Organic Chemistry; vol. 57; nb. 26; (1992); p. 7151 - 7158 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O O

O

OH

HO O O

O HO

OH

O

O O

H

O O

Rx-ID: 19581836 View in Reaxys 74/94 Yield

Conditions & References Reaction Steps: 3 1: 89 percent / 4-(N,N-dimethylamino)pyridine / pyridine-d5 / 0.05 h / 80 °C 2: 89 percent / 3percent methanolic HCl / 16 h / Ambient temperature With hydrogenchloride, dmap in perdeuteriopyridine Wilson; Burk; Biftu; Ball; Hoogsteen; Journal of Organic Chemistry; vol. 57; nb. 26; (1992); p. 7151 - 7158 View in Reaxys

O

O O

O

Br

OH

O

O

O O

O O

O

O

OH

O Br

H O O

Rx-ID: 19582334 View in Reaxys 75/94 Yield

Conditions & References Reaction Steps: 2 1: 89 percent / 3percent methanolic HCl / 16 h / Ambient temperature With hydrogenchloride Wilson; Burk; Biftu; Ball; Hoogsteen; Journal of Organic Chemistry; vol. 57; nb. 26; (1992); p. 7151 - 7158 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

OH

O

OH

O

O

O

H O

HO

H

HO

Rx-ID: 2792917 View in Reaxys 76/94 Yield

Conditions & References Yield given. Multistep reaction. Yields of byproduct given Yu; Simon; Tetrahedron; vol. 47; nb. 43; (1991); p. 9035 - 9052 View in Reaxys

O

O

O

H

OH

H

Rx-ID: 2199186 View in Reaxys 77/94 Yield

Conditions & References

92 %

With lipase from Candida cylindracea, Time= 4.5h, Ambient temperature, 0.1 M phosphate buffer, pH 7.0 Delnick, Deborah L.; Margolin, Alexey L.; Tetrahedron Letters; vol. 31; nb. 47; (1990); p. 6797 - 6798 View in Reaxys

O

O

O

OH

H

Rx-ID: 21676783 View in Reaxys 78/94 Yield

Conditions & References Reaction Steps: 2 1: 44 percent / lipase from Pseudomonas sp. (Amano) / 3 h / Ambient temperature; 0.1 phosphate buffer, pH 7.0 2: 92 percent / lipase from Candida cylindracea / 4.5 h / Ambient temperature; 0.1 M phosphate buffer, pH 7.0 With lipase from Candida cylindracea, lipase from Pseudomonas sp. (Amano) Delnick, Deborah L.; Margolin, Alexey L.; Tetrahedron Letters; vol. 31; nb. 47; (1990); p. 6797 - 6798 View in Reaxys

O

OH

N O

H

O N

Si

Rx-ID: 3760449 View in Reaxys 79/94

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

Yield

Conditions & References With hydrogen, titanium tetrachloride, palladium dichloride, 1) CH2Cl2, -78 deg C, 2 h, then -40 deg C, 2 h, 2) CH3COOH, Multistep reaction Gennari, Cesare; Venturini, Isabella; Gislon, Gabriele; Schimperna, Giuliana; Tetrahedron Letters; vol. 28; nb. 2; (1987); p.

227 - 230 View in Reaxys With hydrogen, titanium tetrachloride, palladium dichloride, 1.) CH2Cl2, -78 - -40 deg C, 3 h; 2.) AcOH, 5 d, Yield given. Multistep reaction Gennari, Cesare; Schimperna, Giuliana; Venturini, Isabella; Tetrahedron; vol. 44; nb. 13; (1988); p. 4221 - 4232 View in Reaxys

O

OH

O

O H

N

I

HO

H

OH

Rx-ID: 3385499 View in Reaxys 80/94 Yield

Conditions & References With hydrogenchloride, lithium diisopropyl amide, 1.) THF, 0 deg C, 2 h, 2.) dioxane, 90-95 deg C, 42 h, Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

O

OH

O H

O

HO

H

N HO

Rx-ID: 3499086 View in Reaxys 81/94 Yield

Conditions & References With hydrogenchloride in 1,4-dioxane, Time= 42h, T= 90 - 95 °C , Yield given. Yields of byproduct given. Title compound not separated from byproducts Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

O

H

OH

H

N

O

O

Rx-ID: 19199537 View in Reaxys 82/94 Yield

Conditions & References Reaction Steps: 3 1: 83 percent / Mg / diethyl ether / reflux, 4 h -> ambient temperature 2: LDA / tetrahydrofuran / -100 deg C, 2 h -> -50 deg C 3: 3 M aq. HCl / dioxane / 42 h / 90 - 95 °C With hydrogenchloride, magnesium, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane, diethyl ether Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

O

OH

H

O

N OH

Rx-ID: 19210596 View in Reaxys 83/94 Yield

Conditions & References Reaction Steps: 2 1: LDA / tetrahydrofuran / -100 deg C, 2 h -> -50 deg C 2: 3 M aq. HCl / dioxane / 42 h / 90 - 95 °C With hydrogenchloride, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane Guoqiang, Lin; Hjalmarsson, Mats; Hoegberg, Hans-Erik; Jernstedt, Karen; Norin, Torbjoern; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 38; nb. 9; (1984); p. 795 - 802 View in Reaxys

O

O

O

OH

H

Rx-ID: 2774511 View in Reaxys 84/94 Yield

Conditions & References With hydrogen Evans, D. A.; Ennis, M. D.; Mathre, D. J.; Journal of the American Chemical Society; vol. 104; nb. 6; (1982); p. 1737 - 1739 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

O

OH

H

aq.-ethanolic KOH Br

Rx-ID: 19455142 View in Reaxys 85/94 Yield

Conditions & References Reaction Steps: 3 1: 1.) LiN(i-C3H7)2 / 1.) THF, -78 deg C, 2.) 0 deg C, 4 h 2: 93 percent / PhCH2OH / tetrahydrofuran / 1 h / 0 °C 3: hydrogen With hydrogen, benzyl alcohol, lithium diisopropyl amide in tetrahydrofuran Evans, D. A.; Ennis, M. D.; Mathre, D. J.; Journal of the American Chemical Society; vol. 104; nb. 6; (1982); p. 1737 - 1739 View in Reaxys

O

O

O

O

OH

H

O

Rx-ID: 19468132 View in Reaxys 86/94 Yield

Conditions & References Reaction Steps: 3 2: 93 percent / PhCH2OH / tetrahydrofuran / 1 h / 0 °C 3: hydrogen With hydrogen, benzyl alcohol in tetrahydrofuran Evans, D. A.; Ennis, M. D.; Mathre, D. J.; Journal of the American Chemical Society; vol. 104; nb. 6; (1982); p. 1737 - 1739 View in Reaxys

O

O–

O

Na +

OH

H

Rx-ID: 3006378 View in Reaxys 87/94 Yield 95 %

Conditions & References With phosphate buffer, ethylenediaminetetraacetic acid, Time= 12h, enoat-reductase Simon, Helmut; Guenther, Helmut; Bader, Johann; Tischer, Wilhelm; Angewandte Chemie; vol. 93; nb. 10; (1981); p. 897 898 View in Reaxys

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

OH

O

H

O

N OH

Rx-ID: 2658424 View in Reaxys 88/94 Yield

Conditions & References

92 %

With hydrogenchloride, Time= 2h, T= 100 °C Evans, D. A.; Takacs, J. M.; Tetrahedron Letters; vol. 21; (1980); p. 4233 - 4236 View in Reaxys

O

OH

H Br

Rx-ID: 21560605 View in Reaxys 89/94 Yield

Conditions & References Reaction Steps: 2 1: 1.) LDA, THF, 25 deg C, 2.) -100 deg C 2: 92 percent / 1.0 N HCl / 2 h / 100 °C With hydrogenchloride Evans, D. A.; Takacs, J. M.; Tetrahedron Letters; vol. 21; (1980); p. 4233 - 4236 View in Reaxys

O

(+-)-2-methyl-3-phenyl-propionic acid

OH

H

Rx-ID: 7625857 View in Reaxys 90/94 Yield

Conditions & References With Quinine DeTar; Weis; Journal of the American Chemical Society; vol. 79; (1957); p. 3045,3048 View in Reaxys

O

H 2N

OH

H H

(+-)-2-methyl-3-phenyl-propionic acid

Rx-ID: 7625858 View in Reaxys 91/94 Yield

Conditions & References Schrecker; Journal of Organic Chemistry; vol. 22; (1957); p. 33

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(R)-alpha-Methylhydrocinnamic acid [C10H12O2]

View in Reaxys

O

(R)-2-methyl-3-phenyl-propionitrile

aq.-ethanolic NaOH-solution

OH

H

Rx-ID: 7625859 View in Reaxys 92/94 Yield

Conditions & References Kenyon; Phillips; Pittman; Journal of the Chemical Society; (1935); p. 1079 View in Reaxys

O

OH

H

η-methyl-η-benzyl-acetoacetic acid ester

Rx-ID: 7625856 View in Reaxys 93/94 Yield

Conditions & References With potassium hydroxide Jones; Wallis; Journal of the American Chemical Society; vol. 48; (1926); p. 180 View in Reaxys

O

O

HO

OH

H

Rx-ID: 438147 View in Reaxys 94/94 Yield

Conditions & References With Quinine Kipping; Hunter; Journal of the Chemical Society; vol. 83; (1903); p. 1007 View in Reaxys

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