(S)-2-Amino-2-methyl-3-phenylpropanoic acid [C10H13NO2]

Query Query

O

1. Query

Results

Date

109 reactions in Reaxys

2018-03-20 14h:45m:08s (EST)

HO H 2N

Search as: As drawn AND (IDE.XRN=2803962)

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Cl

(v4) (v3)

N– O

N

N

Ni 2+ – (v4)O (v4) (v2) N

O

O

O

HO

NH

H 2N Cl

O

R(a)-isomer

Rx-ID: 42593868 View in Reaxys 1/109 Yield 59 %, 100 %

Conditions & References Ni (II) complex (190.0 mg, 0.242 mmol) with α- methyl -L- phenylalanine moiety of methanol (5.7 mL) suspension 1N hydrochloric acid (1.2 mL, 1.20 mmol, 5 eq.)was added and the mixture was stirred for 5 hours at 40-50 ° C on.The reaction mixture was concentrated under reduced pressure, dichloromethane to the residue after (10 mL) and dissolved by adding water (10 mL) separated into layers, an organic layer 2percent aqueous ammonia (10 mL, 2 times), water ( 10 mL, 2 times), followed by washing with saturated brine (10 mL, 2 times), dried over sodium sulfate, the solvent was distilled off, chiral auxiliary (R body) (138.2 mg, chemical purity 92.2percent) was quantitatively recovered. On the other hand, was dissolved in a mixed solvent of the aqueous layer obtained was concentrated to dryness solids 8percent aqueous ammonia (0.5 mL) and methanol (5.0 mL), a cation-exchange resin column (SK-1B, 40 mL, eluent: water, through followed by 4percent aqueous ammonia) to give α- methyl -L- phenylalanine (25.6 mg, yield 59.0percent) as a white solid.The resulting α- methyl -L- phenylalanine (20.0 mg, 0.112 mmol) was suspended in dry acetonitrile (1.0 mL), tetramethylammonium hydroxide pentahydrate (20.2 mg, 0.112 mmol) at room temperature by the addition of in and stirred for one hour, (Boc) 2was stirred for 76 hours at room temperature by the addition ofO (36.5 mg, 0.167 mmol) .The reaction solution was obtained by concentrating the residue was washed twice with water (5 mL) to dissolve to isopropyl ether (2 mL), after adjusted to pH 3 by adding citric acid to the aqueous layer, water the layers were extracted 3 times with ethyl acetate (10 mL).The combined organic layers were washed with water (5 of 5 mL, 2 times) and saturated brine (5 of 5 mL, 2 times), dried over magnesium sulfate, the solvent was distilled off Boc-α-methyl -L- phenylalanine ( 29.3 mg, 55.5percent yield chemical purity 91.3percent, the ee 99.6percent) as a colorless oily substance.

With hydrogenchloride in methanol, water, Time= 5h, T= 40 - 50 °C Patent; Ha mariya kuching kogok Corporation; Moriwaki, Hiroshi; Kawashima, Aki; Takeda, Ryosuke; Kawamura, Akiy; Solo, Syonok Vadim A.; (90 pag.); KR2015/133268; (2015); (A) Korean View in Reaxys

59 %

3.2 : Release of α-methyl-L-phenylalanine from Nickel (II) Complex Having α-methyl-L-phenylalanine Moiety Under Acidic Conditions and Protection of α-methyl-L-phenylalanine with Boc Group Example 3-2 Release of α-methyl-L-phenylalanine from Nickel (II) Complex Having α-methyl-L-phenylalanine Moiety Under Acidic Conditions and Protection of α-methyl-L-phenylalanine with Boc Group To a suspension of a nickel (II) complex having an α-methyl-L-phenylalanine moiety (190.0 mg, 0.242 mmol) in methanol (5.7 mL), 1 N hydrochloric acid (1.2 mL, 1.20 mmol, 5 eq.) was added, and the mixture was stirred at 40 to 50° C. for 5 hours.

The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in dichloromethane (10 mL) and water (10 mL).

After phase separation, the organic layer was washed with 2percent aqueous ammonia (10 mL, twice), with water (10 mL, twice), and then with saturated brine (10 mL, twice).

The organic layer was dried over sodium sulfate, and then the solvent was removed by evaporation to give quantitatively a chiral auxiliary (R-isomer) (138.2 mg, chemical purity: 92.2percent).

Meanwhile, the aqueous layer was concentrated to dryness, and the resulting solid was dissolved in a mixed solvent of 8percent aqueous ammonia (0.5 mL) and methanol (5.0 mL).

The solution was passed through a cation exchange resin column [SK-1B, 40 mL, eluent: water and subsequently 4percent aqueous ammonia] to give α-methyl-L-phenylalanine (25.6 mg, yield: 59.0percent) as a white solid.

With hydrogenchloride, water in methanol, Time= 5h, T= 50 °C

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Patent; HAMARI CHEMICALS, LTD.; Moriwaki, Hiroki; Kawashima, Aki; Takeda, Ryosuke; Kawamura, Akie; Soloshonok, Vadim A.; (74 pag.); US2016/102045; (2016); (A1) English View in Reaxys

O

O

OH

O N

NH 2

I

H

O HO

H 2N

Rx-ID: 44917278 View in Reaxys 2/109 Yield

Conditions & References 2 :N-benzylidenebis-phenylalanine tert-butyl (15.5 mg, 50μmol) (3) in a toluene solution (2.5 ml) (S)-Maruoka catalyst (registered trademark; nagase Co. ; (CAS: 851942-89-7) (18.7 mg, 25μmol) is added, 0 °C cooled by ice bath.

An argon atmosphere, adding aq. unsatd. cesium hydroxide (3.75g), 30 minutes at 0 °C is violently agitated. The methyl iodide of 50 mm prepared by adding a toluene solution (40μL, 2μmol), argon atmosphere, a vigorous stirring at 0° C (methyl iodide is added and a reaction start point). In HPLC perfluoroalkylated for confirming the progress of the reaction, the reaction from 5 minutes after the start, after 10 minutes, after 15 minutes, 20 minutes after the sampling is performed and, by calculating a conversion rate of methyl iodide HPLC analysis. The result of monitoring is confirmed by HPLC before the reaction, the reaction mixture from the starting reaction (5 ml) 25 minutes after pouring water, organic layer separates politeness. The optical part (100μL) extracted org. sampled for checking the purity, the remaining organic layer is heated to 60 °C 4N hydrochloric acid (2.5 ml, 10mmol) in addition to, a vigorous stirring at 60° C (after 30 minutes from the start of reaction). With the progress of the hydrolysis reaction for HPLC, in addition to the organic layer is from 5 minutes after 4N hydrochloric acid solution, after 10 minutes, after 15 minutes, 20 minutes after the sampling is performed and, by HPLC analysis, reaction intermediate and tert-butyl biphenylalanine dimethylpolysiloxaness α-α-conversion rate is calculated from a ratio of dalanine dimethylpolysiloxaness-. In addition to the organic layer 25 minutes after 4N hydrochloric acid solution from the agitation is stopped, by separating the water layer, and a purpose compd. (4) (- (S)-α dimethylpolysiloxaness biphenylalanine) obtained as an aqueous solution of a reaction mixture (60 minutes after the start of reaction). In this embodiment, α-methyl iodide biphenylalanine dimethylpolysiloxaness obtained from 94percent yield conversioin.In this embodiment, the optical obtd. compd. for measuring purity, sampled hydroxycitric aq. 1M (0.5 ml) is added to the organic layer, 30 minutes after stirring, tert-butyl ether (0.5 ml) in a washer 3 times. The separated water layer and sodium carbonate (100 mg), ethyl acetate (0.5 ml) is added, 10 min. The organic layer separating, concentrating, hexane/2-propanol concentrated residue is added to the mixed solution of (80/20) (1 ml), and the sample solution, analyzed by HPLC a [Daicel Chiralpak AD-H; eluent: Phenylbicyclohexane/2-propanol = 30/1, velocity 0.5 ml/min; holding time : (R) body = 13.6 min, the body (S) = 20.4 min]. In this embodiment, the purity of the obtained optical 89percent ee. Furthermore, in this embodiment, the conversion rate cycloalkylation obtd. in Table 3, the hydrolysis reaction of the conversion rate is shown in Table 4.

Stage 1: With (11bS)-(-)-4,4-dibutyl-4,5-dihydro-2,6-bis(3,4,5-trifluorophenyl)-3H-dinaphth[2,1-c:1′,2′-e]azepinium bromide, cesium hydroxide in toluene, Time= 0.5h, T= 0 °C , Inert atmosphere Stage 2: With hydrogenchloride in water, toluene, Time= 0.5h, T= 60 °C , Inert atmosphere, stereoselective reaction Patent; Nagase Co., Ltd.; RIKEN; Yamamoto, Kenichiro; Kodama, Kazuya; Anzai, Kinsei; Matsuyama, Keisuke; Sasano, Arisue; Hashizume, Yoshinobu; Hume, William Yuwan; Yashio, Keiji; Nozaki, Satoshi; (75 pag.); JP2016/74605; (2016); (A) Japanese View in Reaxys

O

O HO

OH NH 2

O HO

H 2N

H 2N

Rx-ID: 38033763 View in Reaxys 3/109 Yield

Conditions & References With Merck RP-18 WF254S plates coated with Nτ-n-decyl-L-spinacine and Cu acetate in methanol, water, Resolution of racemate

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Remelli, Maurizio; Faccini, Stefania; Conato, Chiara; Chirality; vol. 26; nb. 6; (2014); p. 313 - 318 View in Reaxys

O HO

O HO

H 2N

H 2N

Rx-ID: 4726567 View in Reaxys 4/109 Yield

Conditions & References Hulst, Ron; Broxterman, Quirinus B.; Kamphuis, Johan; Formaggio, Fernando; Crisma, Marco; Toniolo, Claudio; Kellogg, Richard M.; Tetrahedron Asymmetry; vol. 8; nb. 12; (1997); p. 1987 - 1999 View in Reaxys With cinchonidine Drabina, Pavel; Karel, Sergej; Panov, Illia; Sedlak, Milos; Tetrahedron Asymmetry; vol. 24; nb. 5-6; (2013); p. 334 - 339 View in Reaxys

O Br

HO

H 2N

Rx-ID: 20993454 View in Reaxys 5/109 Yield

Conditions & References Reaction Steps: 2 1: 84 percent / potassium bis(trimethylsilyl)amide / tetrahydrofuran / 0.5 h / -78 °C 2: 93 percent / H2 / PdCl2 / tetrahydrofuran; ethanol / 48 h / 2585.7 Torr With hydrogen, potassium hexamethylsilazane, palladium dichloride in tetrahydrofuran, ethanol Williams; Im; Journal of the American Chemical Society; vol. 113; nb. 24; (1991); p. 9276 - 9286 View in Reaxys Reaction Steps: 3 1: 1) LDA / 1) THF, -78 deg C, 30 min, 2) -25 deg C, 14 h 2: 1) diphenylphosphoryl azide, NEt3 / 1) benzene, reflux, 2 h, 2) reflux, 20 h 3: KOH, 18-crown-6 / 24 h / Heating With potassium hydroxide, 18-crown-6 ether, diphenylphosphoranyl azide, triethylamine, lithium diisopropyl amide Ihara, Masataka; Takahashi, Masanobu; Taniguchi, Nobuaki; Yasui, Ken; Niitsuma, Hiroko; Fukumoto, Keiichiro; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); nb.

3; (1991); p. 525 - 535 View in Reaxys Reaction Steps: 3 1.1: lithium chloride; lithium diisopropyl amide / tetrahydrofuran / 0.25 h / -78 - 0 °C / Inert atmosphere 1.2: 3.5 h / -50 °C / Inert atmosphere 2.1: hydrogenchloride / tetrahydrofuran; water / 3 h / 23 °C / Inert atmosphere 3.1: water / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere With hydrogenchloride, water, lithium chloride, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane, water Hugelshofer, Cedric L.; Mellem, Kevin T.; Myers, Andrew G.; Organic Letters; vol. 15; nb. 12; (2013); p. 3134 3137 View in Reaxys Reaction Steps: 3 1.1: lithium chloride; lithium diisopropyl amide / tetrahydrofuran / 0.25 h / -78 - 0 °C / Inert atmosphere 1.2: 3.5 h / -50 °C / Inert atmosphere 2.1: hydrogenchloride / tetrahydrofuran; water / 3 h / 23 °C / Inert atmosphere 3.1: water / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere With hydrogenchloride, water, lithium chloride, lithium diisopropyl amide in tetrahydrofuran, 1,4-dioxane, water

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Hugelshofer, Cedric L.; Mellem, Kevin T.; Myers, Andrew G.; Organic Letters; vol. 15; nb. 12; (2013); p. 3134 3137 View in Reaxys

O

O HO

H 2N

Rx-ID: 35129152 View in Reaxys 6/109 Yield

Conditions & References Reaction Steps: 3 1: ammonia 2: hydrogenchloride; water 3: cinchonidine With hydrogenchloride, cinchonidine, ammonia, water, 1: |Strecker Aminoacid Synthesis Drabina, Pavel; Karel, Sergej; Panov, Illia; Sedlak, Milos; Tetrahedron Asymmetry; vol. 24; nb. 5-6; (2013); p. 334 - 339 View in Reaxys

O

N

HO

H 2N

H 2N

Rx-ID: 35129159 View in Reaxys 7/109 Yield

Conditions & References Reaction Steps: 2 1: hydrogenchloride; water 2: cinchonidine With hydrogenchloride, cinchonidine, water Drabina, Pavel; Karel, Sergej; Panov, Illia; Sedlak, Milos; Tetrahedron Asymmetry; vol. 24; nb. 5-6; (2013); p. 334 - 339 View in Reaxys

O N

O

NE

HO

OH

H 2N

Rx-ID: 35847947 View in Reaxys 8/109 Yield

Conditions & References Reaction Steps: 2 1: hydrogenchloride / tetrahydrofuran; water / 3 h / 23 °C / Inert atmosphere 2: water / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere With hydrogenchloride, water in tetrahydrofuran, 1,4-dioxane, water Hugelshofer, Cedric L.; Mellem, Kevin T.; Myers, Andrew G.; Organic Letters; vol. 15; nb. 12; (2013); p. 3134 3137 View in Reaxys

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O

HO

OH

OH

H

O

NH 2

N

NH

H 2N

H

Rx-ID: 35847981 View in Reaxys 9/109 Yield

Conditions & References

460 mg, 583 mg

With water in 1,4-dioxane, Time= 3h, T= 100 °C , Inert atmosphere Hugelshofer, Cedric L.; Mellem, Kevin T.; Myers, Andrew G.; Organic Letters; vol. 15; nb. 12; (2013); p. 3134 3137 View in Reaxys

O

O

NE

N

HO

OH

H 2N

Rx-ID: 35848200 View in Reaxys 10/109 Yield

Conditions & References Reaction Steps: 2 1: hydrogenchloride / tetrahydrofuran; water / 3 h / 23 °C / Inert atmosphere 2: water / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere With hydrogenchloride, water in tetrahydrofuran, 1,4-dioxane, water Hugelshofer, Cedric L.; Mellem, Kevin T.; Myers, Andrew G.; Organic Letters; vol. 15; nb. 12; (2013); p. 3134 3137 View in Reaxys

H

H

O

N

O

O HO

H 2N

Rx-ID: 30764058 View in Reaxys 11/109 Yield 86 %

Conditions & References Stage 1: With cesium hydroxide, water in ethanol, Time= 2h, T= 70 °C Stage 2: With hydrogenchloride in water Lu, Ta-Jung; Lin, Cheng-Kun; Journal of Organic Chemistry; vol. 76; nb. 6; (2011); p. 1621 - 1633 View in Reaxys

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O

O

N N

HO O

H 2N

Rx-ID: 29616192 View in Reaxys 12/109 Yield

Conditions & References

Ca. 100 %

With water, hydrogen iodide, Reflux Balducci, Daniele; Lazzari, Ilaria; Monari, Magda; Piccinelli, Fabio; Porzi, Gianni; Amino Acids; vol. 38; nb. 3; (2010); p. 829 - 837 View in Reaxys

H

O

HO

NH 2

Br

HO

O

H 2N

Rx-ID: 30183987 View in Reaxys 13/109 Yield

Conditions & References Stage 1: With (S)-N-(2-benzoylphenyl)-1-(2-fluorobenzyl)pyrrolidine-2-carboxamide, sodium methylate, nickel(II) nitrate in methanol, T= 50 °C Stage 2: With sodium hydroxide in N,N-dimethyl-formamide, Time= 0.133333h, T= 45 - 50 °C , Inert atmosphere, optical yield given as percent ee, enantioselective reaction, Further stages Saghyan, Ashot S.; Dadayan, Ani S.; Dadayan, Slavik A.; Mkrtchyan, Anna F.; Geolchanyan, Arpine V.; Manasyan, Luiza L.; Ajvazyan, Hrant R.; Khrustalev, Victor N.; Hambardzumyan, Hasmik H.; Maleev, Victor I.; Tetrahedron Asymmetry; vol. 21; nb. 24; (2010); p. 2956 - 2965 View in Reaxys

O

O O

HO

H 2N

H 2N

Rx-ID: 28536154 View in Reaxys 14/109 Yield

Conditions & References

100 %

Stage 1: With lithium hydroxide monohydrate in ethanol, water, Time= 48h, T= 25 °C Stage 2: With hydrogenchloride in ethanol, water, pH= 2, optical yield given as percent ee Green, Jonathan E.; Bender, David M.; Jackson, Stona; O'donnell, Martin J.; Mccarthy, James R.; Organic Letters; vol. 11; nb. 4; (2009); p. 807 - 810 View in Reaxys

N

H

O

O O

HO

H 2N

Rx-ID: 10254542 View in Reaxys 15/109 Yield 88 %

Conditions & References Stage 1: With sodium hydroxide in methanol, acetone, Time= 2h, T= 20 °C Stage 2: With hydrogenchloride, Time= 3h, T= 92 °C Xu, Peng-Fei; Li, Shuo; Lu, Ta-Jung; Wu, Chen-Chang; Fan, Botao; Golfis, Georgia; Journal of Organic Chemistry; vol. 71; nb. 12; (2006); p. 4364 - 4373 View in Reaxys

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H

O

O

O N

HO

H 2N

Rx-ID: 10255148 View in Reaxys 16/109 Yield

Conditions & References

89 %

Stage 1: With sodium hydroxide in methanol, acetone, Time= 2h, T= 20 °C Stage 2: With hydrogenchloride, Time= 3h, T= 92 °C Xu, Peng-Fei; Li, Shuo; Lu, Ta-Jung; Wu, Chen-Chang; Fan, Botao; Golfis, Georgia; Journal of Organic Chemistry; vol. 71; nb. 12; (2006); p. 4364 - 4373 View in Reaxys

N

H

O

O O

HO

H 2N

Rx-ID: 12259747 View in Reaxys 17/109 Yield

Conditions & References Reaction Steps: 2 1.1: n-BuLi; diisopropylamine / tetrahydrofuran; hexane / 1.5 h / -30 °C 1.2: hexamethylphosphoric triamide / tetrahydrofuran; hexane / -78 °C 1.3: 82 percent / tetrahydrofuran; hexane / 12 h / -78 °C 2.1: aqueous NaOH / methanol; acetone / 2 h / 20 °C 2.2: 88 percent / aqueous HCl / 3 h / 92 °C With sodium hydroxide, n-butyllithium, diisopropylamine in tetrahydrofuran, methanol, hexane, acetone Xu, Peng-Fei; Li, Shuo; Lu, Ta-Jung; Wu, Chen-Chang; Fan, Botao; Golfis, Georgia; Journal of Organic Chemistry; vol. 71; nb. 12; (2006); p. 4364 - 4373 View in Reaxys

Br

O

ZnCr-benzoate*3H2O HO

H 2N

Rx-ID: 12282295 View in Reaxys 18/109 Yield

Conditions & References Reaction Steps: 2 1.1: n-BuLi; diisopropylamine / tetrahydrofuran; hexane / 1.5 h / -30 °C 1.2: hexamethylphosphoric triamide / tetrahydrofuran; hexane / -78 °C 1.3: 91 percent / tetrahydrofuran; hexane / 12 h / -78 °C 2.1: aqueous NaOH / methanol; acetone / 2 h / 20 °C 2.2: 89 percent / aqueous HCl / 3 h / 92 °C With sodium hydroxide, n-butyllithium, diisopropylamine in tetrahydrofuran, methanol, hexane, acetone Xu, Peng-Fei; Li, Shuo; Lu, Ta-Jung; Wu, Chen-Chang; Fan, Botao; Golfis, Georgia; Journal of Organic Chemistry; vol. 71; nb. 12; (2006); p. 4364 - 4373 View in Reaxys Reaction Steps: 2 1.1: n-BuLi; diisopropylamine / tetrahydrofuran; hexane / 1.5 h / -30 °C 1.2: hexamethylphosphoric triamide / tetrahydrofuran; hexane / -78 °C 1.3: 75 percent / tetrahydrofuran; hexane / 12 h / -78 °C 2.1: aqueous NaOH / methanol; acetone / 2 h / 20 °C 2.2: 89 percent / aqueous HCl / 3 h / 92 °C With sodium hydroxide, n-butyllithium, diisopropylamine in tetrahydrofuran, methanol, hexane, acetone

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Xu, Peng-Fei; Li, Shuo; Lu, Ta-Jung; Wu, Chen-Chang; Fan, Botao; Golfis, Georgia; Journal of Organic Chemistry; vol. 71; nb. 12; (2006); p. 4364 - 4373 View in Reaxys

O N

HO O

O

H 2N

Rx-ID: 12292338 View in Reaxys 19/109 Yield

Conditions & References Reaction Steps: 2 1.1: n-BuLi; diisopropylamine / tetrahydrofuran; hexane / 1.5 h / -30 °C 1.2: hexamethylphosphoric triamide / tetrahydrofuran; hexane / -78 °C 1.3: 82 percent / tetrahydrofuran; hexane / 12 h / -78 °C 2.1: aqueous NaOH / methanol; acetone / 2 h / 20 °C 2.2: 88 percent / aqueous HCl / 3 h / 92 °C With sodium hydroxide, n-butyllithium, diisopropylamine in tetrahydrofuran, methanol, hexane, acetone Xu, Peng-Fei; Li, Shuo; Lu, Ta-Jung; Wu, Chen-Chang; Fan, Botao; Golfis, Georgia; Journal of Organic Chemistry; vol. 71; nb. 12; (2006); p. 4364 - 4373 View in Reaxys

H N

O

O

O

HO

N

H 2N

Rx-ID: 3677465 View in Reaxys 20/109 Yield

Conditions & References

94 %

With hydrogenchloride, Time= 2h, Heating Cativiela; Diaz-de-Villegas; Galvez; Tetrahedron Asymmetry; vol. 5; nb. 2; (1994); p. 261 - 268 View in Reaxys

8.06 g

With hydrogenchloride, Time= 36h, Heating Badorrey, Ramon; Cativiela, Carlos; Diaz-de-Villegas, Maria D.; Galvez, Jose A.; Tetrahedron Asymmetry; vol.

14; nb. 15; (2003); p. 2201 - 2207 View in Reaxys

O O

O

HN O

O

HO

H 2N

Rx-ID: 9277216 View in Reaxys 21/109 Yield 95 %

Conditions & References With hydrogenchloride, Time= 3h, Heating Wu, Zhong-Liu; Li, Zu-Yi; Journal of Organic Chemistry; vol. 68; nb. 6; (2003); p. 2479 - 2482 View in Reaxys With hydrogenchloride, Heating Wu, Zhong-Liu; Li, Zu-Yi; Chemical Communications; nb. 3; (2003); p. 386 - 387 View in Reaxys

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O HO

O N HO

N

H 2N

N

Rx-ID: 9348772 View in Reaxys 22/109 Yield

Conditions & References With hydrogen, palladium on activated charcoal in ethanol, Time= 16h, T= 20 °C Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5 View in Reaxys

O

O

O N

HO

H 2N

O

Rx-ID: 9556389 View in Reaxys 23/109 Yield

Conditions & References

91 %

With sodium hydroxide in methanol, water, Time= 72h, T= 60 °C Koch, Claus-Juergen; Simonyiova, Sona; Pabel, Joerg; Kaertner, Annerose; Polborn, Kurt; Wanner, Klaus Theodor; European Journal of Organic Chemistry; nb. 7; (2003); p. 1244 - 1263 View in Reaxys

H N

O

O HO

O O

H 2N

Rx-ID: 9746218 View in Reaxys 24/109 Yield

Conditions & References

7.17 g

With hydrogenchloride, Time= 5h, Heating Badorrey, Ramon; Cativiela, Carlos; Diaz-de-Villegas, Maria D.; Galvez, Jose A.; Tetrahedron Asymmetry; vol.

14; nb. 15; (2003); p. 2201 - 2207 View in Reaxys O

O

O

HO N

H 2N

Rx-ID: 13385632 View in Reaxys 25/109 Yield

Conditions & References Reaction Steps: 6 1.1: K2CO3 / acetone / 12 h / 20 °C 2.1: 17.4 g / KOH / methanol / 1 h / 20 °C 3.1: (1S,2R)-(+)-norephedrine / CHCl3; hexane / Heating 3.2: 38 percent / aq. HCl 4.1: aq. NaOH; aq. H2O2 / 20 °C 5.1: iodobenzene diacetate / methanol / 2 h / 20 °C 6.1: 7.17 g / aq. HCl / 5 h / Heating With hydrogenchloride, potassium hydroxide, sodium hydroxide, [bis(acetoxy)iodo]benzene, (1S,2R)-(+)-norphedrine, dihydrogen peroxide, potassium carbonate in methanol, hexane, chloroform, acetone, 5.1: Hofmann rearrangement Badorrey, Ramon; Cativiela, Carlos; Diaz-de-Villegas, Maria D.; Galvez, Jose A.; Tetrahedron Asymmetry; vol.

14; nb. 15; (2003); p. 2201 - 2207

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View in Reaxys O E

O

O HO

N

H 2N

Rx-ID: 13385758 View in Reaxys 26/109 Yield

Conditions & References Reaction Steps: 7 1.1: H2 / Pd/C / tetrahydrofuran / 24 h / 20 °C / atmospheric pressure 2.1: K2CO3 / acetone / 12 h / 20 °C 3.1: 17.4 g / KOH / methanol / 1 h / 20 °C 4.1: (1S,2R)-(+)-norephedrine / CHCl3; hexane / Heating 4.2: 38 percent / aq. HCl 5.1: aq. NaOH; aq. H2O2 / 20 °C 6.1: iodobenzene diacetate / methanol / 2 h / 20 °C 7.1: 7.17 g / aq. HCl / 5 h / Heating With hydrogenchloride, potassium hydroxide, sodium hydroxide, [bis(acetoxy)iodo]benzene, (1S,2R)-(+)-norphedrine, hydrogen, dihydrogen peroxide, potassium carbonate, palladium on activated charcoal in tetrahydrofuran, methanol, hexane, chloroform, acetone, 6.1: Hofmann rearrangement Badorrey, Ramon; Cativiela, Carlos; Diaz-de-Villegas, Maria D.; Galvez, Jose A.; Tetrahedron Asymmetry; vol.

14; nb. 15; (2003); p. 2201 - 2207 View in Reaxys

O

OH

N

O HO

H 2N

Rx-ID: 13387182 View in Reaxys 27/109 Yield

Conditions & References Reaction Steps: 3 1: aq. NaOH; aq. H2O2 / 20 °C 2: iodobenzene diacetate / methanol / 2 h / 20 °C 3: 7.17 g / aq. HCl / 5 h / Heating With hydrogenchloride, sodium hydroxide, [bis(acetoxy)iodo]benzene, dihydrogen peroxide in methanol, 2: Hofmann rearrangement Badorrey, Ramon; Cativiela, Carlos; Diaz-de-Villegas, Maria D.; Galvez, Jose A.; Tetrahedron Asymmetry; vol.

14; nb. 15; (2003); p. 2201 - 2207 View in Reaxys O

HO N

O HO

H 2N

Rx-ID: 13387190 View in Reaxys 28/109 Yield

Conditions & References Reaction Steps: 4 1.1: (1S,2R)-(+)-norephedrine / CHCl3; hexane / Heating 1.2: 38 percent / aq. HCl 2.1: aq. NaOH; aq. H2O2 / 20 °C 3.1: iodobenzene diacetate / methanol / 2 h / 20 °C 4.1: 7.17 g / aq. HCl / 5 h / Heating With hydrogenchloride, sodium hydroxide, [bis(acetoxy)iodo]benzene, (1S,2R)-(+)-norphedrine, dihydrogen peroxide in methanol, hexane, chloroform, 3.1: Hofmann rearrangement

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Badorrey, Ramon; Cativiela, Carlos; Diaz-de-Villegas, Maria D.; Galvez, Jose A.; Tetrahedron Asymmetry; vol.

14; nb. 15; (2003); p. 2201 - 2207 View in Reaxys O O

O

N

HO

H 2N

Rx-ID: 13389114 View in Reaxys 29/109 Yield

Conditions & References Reaction Steps: 5 1.1: 17.4 g / KOH / methanol / 1 h / 20 °C 2.1: (1S,2R)-(+)-norephedrine / CHCl3; hexane / Heating 2.2: 38 percent / aq. HCl 3.1: aq. NaOH; aq. H2O2 / 20 °C 4.1: iodobenzene diacetate / methanol / 2 h / 20 °C 5.1: 7.17 g / aq. HCl / 5 h / Heating With hydrogenchloride, potassium hydroxide, sodium hydroxide, [bis(acetoxy)iodo]benzene, (1S,2R)-(+)-norphedrine, dihydrogen peroxide in methanol, hexane, chloroform, 4.1: Hofmann rearrangement Badorrey, Ramon; Cativiela, Carlos; Diaz-de-Villegas, Maria D.; Galvez, Jose A.; Tetrahedron Asymmetry; vol.

14; nb. 15; (2003); p. 2201 - 2207 View in Reaxys

OH

O

O H 2N

HO O

H 2N

Rx-ID: 13396880 View in Reaxys 30/109 Yield

Conditions & References Reaction Steps: 2 1: iodobenzene diacetate / methanol / 2 h / 20 °C 2: 7.17 g / aq. HCl / 5 h / Heating With hydrogenchloride, [bis(acetoxy)iodo]benzene in methanol, 1: Hofmann rearrangement Badorrey, Ramon; Cativiela, Carlos; Diaz-de-Villegas, Maria D.; Galvez, Jose A.; Tetrahedron Asymmetry; vol.

14; nb. 15; (2003); p. 2201 - 2207 View in Reaxys Reaction Steps: 2 1.1: K2CO3 / dimethylformamide / 24 h / 20 °C 1.2: Hg(OAc)2; NBS / dimethylformamide / 16 h / 20 °C 2.1: 95 percent / 20 percent aq. HCl / 3 h / Heating With hydrogenchloride, potassium carbonate in N,N-dimethyl-formamide Wu, Zhong-Liu; Li, Zu-Yi; Journal of Organic Chemistry; vol. 68; nb. 6; (2003); p. 2479 - 2482 View in Reaxys Reaction Steps: 3 1: K2CO3 / dimethylformamide / 20 °C 2: Hg(OAc)2; NBS / dimethylformamide / 20 °C 3: aq. HCl / Heating With hydrogenchloride, N-Bromosuccinimide, mercury(II) diacetate, potassium carbonate in N,N-dimethyl-formamide Wu, Zhong-Liu; Li, Zu-Yi; Chemical Communications; nb. 3; (2003); p. 386 - 387 View in Reaxys

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O

O

O N

HO O

H 2N

Rx-ID: 13883949 View in Reaxys 31/109 Yield

Conditions & References Reaction Steps: 2 1: sBuLi / tetrahydrofuran; hexane / -78 °C 2: 91 percent / NaOH / H2O; methanol / 72 h / 60 °C With sodium hydroxide, sec.-butyllithium in tetrahydrofuran, methanol, hexane, water Koch, Claus-Juergen; Simonyiova, Sona; Pabel, Joerg; Kaertner, Annerose; Polborn, Kurt; Wanner, Klaus Theodor; European Journal of Organic Chemistry; nb. 7; (2003); p. 1244 - 1263 View in Reaxys O

H 2N H 2N

O

O

HO

H 2N

Rx-ID: 14257696 View in Reaxys 32/109 Yield

Conditions & References Reaction Steps: 3 1.1: 94 percent / Rodococcus sp. CGMCC 0497 / aq. phosphate buffer / 24 h / 30 °C / pH 7.0 2.1: K2CO3 / dimethylformamide / 24 h / 20 °C 2.2: Hg(OAc)2; NBS / dimethylformamide / 16 h / 20 °C 3.1: 95 percent / 20 percent aq. HCl / 3 h / Heating With hydrogenchloride, Rodococcus sp. CGMCC 0497, potassium carbonate in phosphate buffer, N,N-dimethyl-formamide Wu, Zhong-Liu; Li, Zu-Yi; Journal of Organic Chemistry; vol. 68; nb. 6; (2003); p. 2479 - 2482 View in Reaxys Reaction Steps: 4 1: Rhodococcus sp. CGMCC 0497 2: K2CO3 / dimethylformamide / 20 °C 3: Hg(OAc)2; NBS / dimethylformamide / 20 °C 4: aq. HCl / Heating With hydrogenchloride, N-Bromosuccinimide, Rhodococcus sp. CGMCC 0497, mercury(II) diacetate, potassium carbonate in N,N-dimethyl-formamide Wu, Zhong-Liu; Li, Zu-Yi; Chemical Communications; nb. 3; (2003); p. 386 - 387 View in Reaxys

Br

O

XOOC-CH2-COOX HO

H 2N

Rx-ID: 14258882 View in Reaxys 33/109 Yield

Conditions & References Reaction Steps: 4 1.1: 94 percent / Rodococcus sp. CGMCC 0497 / aq. phosphate buffer / 24 h / 30 °C / pH 7.0 2.1: K2CO3 / dimethylformamide / 24 h / 20 °C 2.2: Hg(OAc)2; NBS / dimethylformamide / 16 h / 20 °C 3.1: 95 percent / 20 percent aq. HCl / 3 h / Heating With hydrogenchloride, Rodococcus sp. CGMCC 0497, potassium carbonate in phosphate buffer, N,N-dimethyl-formamide Wu, Zhong-Liu; Li, Zu-Yi; Journal of Organic Chemistry; vol. 68; nb. 6; (2003); p. 2479 - 2482

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View in Reaxys N

O N

HO

H 2N

Rx-ID: 14344818 View in Reaxys 34/109 Yield

Conditions & References Reaction Steps: 5 1: 8 percent / Rhodococcus sp. CGMCC 0497 / 24 h / 30 °C 2: Rhodococcus sp. CGMCC 0497 3: K2CO3 / dimethylformamide / 20 °C 4: Hg(OAc)2; NBS / dimethylformamide / 20 °C 5: aq. HCl / Heating With hydrogenchloride, N-Bromosuccinimide, Rhodococcus sp. CGMCC 0497, mercury(II) diacetate, potassium carbonate in N,N-dimethyl-formamide Wu, Zhong-Liu; Li, Zu-Yi; Chemical Communications; nb. 3; (2003); p. 386 - 387 View in Reaxys Reaction Steps: 4 1: Rhodococcus sp. CGMCC 0497 / 112 h / 30 °C 2: K2CO3 / dimethylformamide / 20 °C 3: Hg(OAc)2; NBS / dimethylformamide / 20 °C 4: aq. HCl / Heating With hydrogenchloride, N-Bromosuccinimide, Rhodococcus sp. CGMCC 0497, mercury(II) diacetate, potassium carbonate in N,N-dimethyl-formamide Wu, Zhong-Liu; Li, Zu-Yi; Chemical Communications; nb. 3; (2003); p. 386 - 387 View in Reaxys Reaction Steps: 4 1: Rhodococcus sp. CGMCC 0497 / 90 h / 30 °C 2: K2CO3 / dimethylformamide / 20 °C 3: Hg(OAc)2; NBS / dimethylformamide / 20 °C 4: aq. HCl / Heating With hydrogenchloride, N-Bromosuccinimide, Rhodococcus sp. CGMCC 0497, mercury(II) diacetate, potassium carbonate in N,N-dimethyl-formamide Wu, Zhong-Liu; Li, Zu-Yi; Chemical Communications; nb. 3; (2003); p. 386 - 387 View in Reaxys

HO

O

H

HO

H 2N

Rx-ID: 14344867 View in Reaxys 35/109 Yield

Conditions & References Reaction Steps: 7 1: Et3N / tetrahydrofuran / 2 h / 20 °C 2: 50 percent aq. NaOH; cetyltrimethylammonium chloride / 18 h / 80 °C 3: 2 percent aq. HCl / methanol / 2 h / 20 °C 4: K2CO3 / methanol / 0.17 h / 20 °C 5: NaN3; 15-crown-5 / tetrahydrofuran / 12 h / 20 °C 6: Jones' reagent / acetone / 0.25 h / 0 °C 7: H2 / Pd/C / ethanol / 16 h / 20 °C With hydrogenchloride, sodium hydroxide, sodium azide, jones' reagent, 15-crown-5, hydrogen, cetyltrimethylammonium chloride, potassium carbonate, triethylamine, palladium on activated charcoal in tetrahydrofuran, methanol, ethanol, acetone

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Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5 View in Reaxys Reaction Steps: 6 1: Et3N / tetrahydrofuran / 2 h / 20 °C 2: 50 percent aq. NaOH; cetyltrimethylammonium chloride / 18 h / 80 °C 3: 2 percent aq. HCl / methanol / 2 h / 20 °C 4: Jones' reagent / acetone / 0.25 h / 0 °C 5: H2 / Pd/C / ethanol / 16 h / 20 °C With hydrogenchloride, sodium hydroxide, jones' reagent, hydrogen, cetyltrimethylammonium chloride, triethylamine, palladium on activated charcoal in tetrahydrofuran, methanol, ethanol, acetone Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5 View in Reaxys

O

O O H 2N

HO O

H 2N

Rx-ID: 14360696 View in Reaxys 36/109 Yield

Conditions & References Reaction Steps: 2 1: Hg(OAc)2; NBS / dimethylformamide / 20 °C 2: aq. HCl / Heating With hydrogenchloride, N-Bromosuccinimide, mercury(II) diacetate in N,N-dimethyl-formamide Wu, Zhong-Liu; Li, Zu-Yi; Chemical Communications; nb. 3; (2003); p. 386 - 387 View in Reaxys

Cl O

O HO

H 2N

Rx-ID: 14372940 View in Reaxys 37/109 Yield

Conditions & References Reaction Steps: 3 1: NaN3; 15-crown-5 / tetrahydrofuran / 12 h / 20 °C 2: Jones' reagent / acetone / 0.25 h / 0 °C 3: H2 / Pd/C / ethanol / 16 h / 20 °C With sodium azide, jones' reagent, 15-crown-5, hydrogen, palladium on activated charcoal in tetrahydrofuran, ethanol, acetone Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5 View in Reaxys

N

N O

N

O HO

H 2N

Rx-ID: 14373004 View in Reaxys 38/109 Yield

Conditions & References Reaction Steps: 2 1: Jones' reagent / acetone / 0.25 h / 0 °C 2: H2 / Pd/C / ethanol / 16 h / 20 °C With jones' reagent, hydrogen, palladium on activated charcoal in ethanol, acetone Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5

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View in Reaxys

O

Cl Cl

HO

HO

H 2N

Rx-ID: 14373063 View in Reaxys 39/109 Yield

Conditions & References Reaction Steps: 4 1: K2CO3 / methanol / 0.17 h / 20 °C 2: NaN3; 15-crown-5 / tetrahydrofuran / 12 h / 20 °C 3: Jones' reagent / acetone / 0.25 h / 0 °C 4: H2 / Pd/C / ethanol / 16 h / 20 °C With sodium azide, jones' reagent, 15-crown-5, hydrogen, potassium carbonate, palladium on activated charcoal in tetrahydrofuran, methanol, ethanol, acetone Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5 View in Reaxys Reaction Steps: 3 1: Jones' reagent / acetone / 0.25 h / 0 °C 2: H2 / Pd/C / ethanol / 16 h / 20 °C With jones' reagent, hydrogen, palladium on activated charcoal in ethanol, acetone Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5 View in Reaxys

Si

O

O HO

H 2N

Rx-ID: 14373069 View in Reaxys 40/109 Yield

Conditions & References Reaction Steps: 6 1: 50 percent aq. NaOH; cetyltrimethylammonium chloride / 18 h / 80 °C 2: 2 percent aq. HCl / methanol / 2 h / 20 °C 3: K2CO3 / methanol / 0.17 h / 20 °C 4: NaN3; 15-crown-5 / tetrahydrofuran / 12 h / 20 °C 5: Jones' reagent / acetone / 0.25 h / 0 °C 6: H2 / Pd/C / ethanol / 16 h / 20 °C With hydrogenchloride, sodium hydroxide, sodium azide, jones' reagent, 15-crown-5, hydrogen, cetyltrimethylammonium chloride, potassium carbonate, palladium on activated charcoal in tetrahydrofuran, methanol, ethanol, acetone Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5 View in Reaxys Reaction Steps: 5 1: 50 percent aq. NaOH; cetyltrimethylammonium chloride / 18 h / 80 °C 2: 2 percent aq. HCl / methanol / 2 h / 20 °C 3: Jones' reagent / acetone / 0.25 h / 0 °C 4: H2 / Pd/C / ethanol / 16 h / 20 °C With hydrogenchloride, sodium hydroxide, jones' reagent, hydrogen, cetyltrimethylammonium chloride, palladium on activated charcoal in methanol, ethanol, acetone Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5 View in Reaxys

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Cl Cl

O O HO

Si

H 2N

Rx-ID: 14373420 View in Reaxys 41/109 Yield

Conditions & References Reaction Steps: 5 1: 2 percent aq. HCl / methanol / 2 h / 20 °C 2: K2CO3 / methanol / 0.17 h / 20 °C 3: NaN3; 15-crown-5 / tetrahydrofuran / 12 h / 20 °C 4: Jones' reagent / acetone / 0.25 h / 0 °C 5: H2 / Pd/C / ethanol / 16 h / 20 °C With hydrogenchloride, sodium azide, jones' reagent, 15-crown-5, hydrogen, potassium carbonate, palladium on activated charcoal in tetrahydrofuran, methanol, ethanol, acetone Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5 View in Reaxys Reaction Steps: 4 1: 2 percent aq. HCl / methanol / 2 h / 20 °C 2: Jones' reagent / acetone / 0.25 h / 0 °C 3: H2 / Pd/C / ethanol / 16 h / 20 °C With hydrogenchloride, jones' reagent, hydrogen, palladium on activated charcoal in methanol, ethanol, acetone Masaki, Yukio; Arasaki, Hideki; Iwata, Masashi; Chemistry Letters; vol. 32; nb. 1; (2003); p. 4 - 5 View in Reaxys O O

O NE

OH

I

NH 2

O

OH

HO

H 2N

Rx-ID: 9174601 View in Reaxys 42/109 Yield

Conditions & References Stage 1: With tetrachlorobis(tetrahydrofuran)titanium(IV), (2R,3R)-1,4-dimethoxy-1,1,4,4-tetraphenyl-2,3-butandiol, lithium diisopropyl amide in tetrahydrofuran, Time= 0.5h, T= -60 °C Stage 2: in tetrahydrofuran, Time= 12h, T= -15 °C Stage 3: With hydrogenchloride in tetrahydrofuran, water, Time= 10h, Heating Hu, Ai-Guo; Zhang, Ling-Yun; Wang, Shan-Wei; Wang, Ji-Tao; Synthetic Communications; vol. 32; nb. 14; (2002); p. 2143 - 2147 View in Reaxys

O

O NH HO

O

HO

H 2N

Rx-ID: 9209108 View in Reaxys 43/109 Yield 80.3 %

Conditions & References With hydrogenchloride, Time= 10h, Heating Shiraiwa, Tadashi; Suzuki, Masahiro; Sakai, Yoshio; Nagasawa, Hisashi; Takatani, Kazuhiro; Noshi, Daisuke; Yamanashi, Kenji; Chemical and pharmaceutical bulletin; vol. 50; nb. 10; (2002); p. 1362 - 1366 View in Reaxys

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{N-({(2S)-2-[1-(3,4-dichlorobenzyl)pyrrolidine-2-carboxamido]phenyl}(phenyl)methylidene)-(S)-2-benzylalaninatoN,N',N'',O}nickel(II)

O HO

H 2N

Rx-ID: 9292633 View in Reaxys 44/109 Yield

Conditions & References

85 %

Acid hydrolysis Belokon; Maleev; Petrosyan; Savel'eva; Ikonnikov; Peregudov; Khrustalev; Saghiyan; Russian Chemical Bulletin; vol. 51; nb. 8; (2002); p. 1593 - 1599 View in Reaxys

O

{N-({(2S)-2-[1-(4-iPrO-2,3,5,6-tetrafluorobenzyl)pyrrolidine-2carboxamido]phenyl}(phenyl)methylidene)-(S)-alaninatoN,N',N'',O}nickel(II)

Br

OH NH 2

O HO

H 2N

Rx-ID: 9292634 View in Reaxys 45/109 Yield

Conditions & References Stage 1: With sodium hydride in N,N-dimethyl-formamide Stage 2:Acid hydrolysis Belokon; Maleev; Petrosyan; Savel'eva; Ikonnikov; Peregudov; Khrustalev; Saghiyan; Russian Chemical Bulletin; vol. 51; nb. 8; (2002); p. 1593 - 1599 View in Reaxys

{N-({(2S)-2-[1-(4-MeO-C6F4CH2)pyrrolidine-2-carboxamido]phenyl}(phenyl)methylidene)-(S)-2-benzylalaninato-N,N',N'',O}nickel(II)

O HO

H 2N

Rx-ID: 9292636 View in Reaxys 46/109 Yield

Conditions & References

79 %

Acid hydrolysis Belokon; Maleev; Petrosyan; Savel'eva; Ikonnikov; Peregudov; Khrustalev; Saghiyan; Russian Chemical Bulletin; vol. 51; nb. 8; (2002); p. 1593 - 1599 View in Reaxys

O

N O O

HO

H 2N

Rx-ID: 14517983 View in Reaxys 47/109 Yield

Conditions & References Reaction Steps: 5 1.1: 121 g / pyridine / H2O / 12 h / 20 °C 2.1: aq. NaOH / dioxane / 1 h / 20 °C 2.2: cinchonidine / ethanol / 6 h 2.3: aq. HCl / 0.5 h 3.1: 90 percent / pyridine / 72 h / 5 °C 4.1: 72.4 percent / NaI; Zn / dimethylformamide / 10 h / 120 °C 5.1: 80.3 percent / HCl / 10 h / Heating With pyridine, hydrogenchloride, sodium hydroxide, sodium iodide, zinc in 1,4-dioxane, water, N,N-dimethyl-formamide Shiraiwa, Tadashi; Suzuki, Masahiro; Sakai, Yoshio; Nagasawa, Hisashi; Takatani, Kazuhiro; Noshi, Daisuke; Yamanashi, Kenji; Chemical and pharmaceutical bulletin; vol. 50; nb. 10; (2002); p. 1362 - 1366

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View in Reaxys

O H

O NH

HO

O

HO

H 2N

Rx-ID: 14518327 View in Reaxys 48/109 Yield

Conditions & References Reaction Steps: 6 1.1: Ac2O / 1 h / 95 °C 2.1: 121 g / pyridine / H2O / 12 h / 20 °C 3.1: aq. NaOH / dioxane / 1 h / 20 °C 3.2: cinchonidine / ethanol / 6 h 3.3: aq. HCl / 0.5 h 4.1: 90 percent / pyridine / 72 h / 5 °C 5.1: 72.4 percent / NaI; Zn / dimethylformamide / 10 h / 120 °C 6.1: 80.3 percent / HCl / 10 h / Heating With pyridine, hydrogenchloride, sodium hydroxide, acetic anhydride, sodium iodide, zinc in 1,4-dioxane, water, N,N-dimethyl-formamide Shiraiwa, Tadashi; Suzuki, Masahiro; Sakai, Yoshio; Nagasawa, Hisashi; Takatani, Kazuhiro; Noshi, Daisuke; Yamanashi, Kenji; Chemical and pharmaceutical bulletin; vol. 50; nb. 10; (2002); p. 1362 - 1366 View in Reaxys

O

O

NH

O

O

HO O

H 2N

Rx-ID: 14527005 View in Reaxys 49/109 Yield

Conditions & References Reaction Steps: 4 1.1: aq. NaOH / dioxane / 1 h / 20 °C 1.2: cinchonidine / ethanol / 6 h 1.3: aq. HCl / 0.5 h 2.1: 90 percent / pyridine / 72 h / 5 °C 3.1: 72.4 percent / NaI; Zn / dimethylformamide / 10 h / 120 °C 4.1: 80.3 percent / HCl / 10 h / Heating With pyridine, hydrogenchloride, sodium hydroxide, sodium iodide, zinc in 1,4-dioxane, N,N-dimethyl-formamide Shiraiwa, Tadashi; Suzuki, Masahiro; Sakai, Yoshio; Nagasawa, Hisashi; Takatani, Kazuhiro; Noshi, Daisuke; Yamanashi, Kenji; Chemical and pharmaceutical bulletin; vol. 50; nb. 10; (2002); p. 1362 - 1366 View in Reaxys

O OH NH HO

O

O HO

H 2N

Rx-ID: 14528504 View in Reaxys 50/109 Yield

Conditions & References Reaction Steps: 3 1: 90 percent / pyridine / 72 h / 5 °C 2: 72.4 percent / NaI; Zn / dimethylformamide / 10 h / 120 °C 3: 80.3 percent / HCl / 10 h / Heating With pyridine, hydrogenchloride, sodium iodide, zinc in N,N-dimethyl-formamide

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Shiraiwa, Tadashi; Suzuki, Masahiro; Sakai, Yoshio; Nagasawa, Hisashi; Takatani, Kazuhiro; Noshi, Daisuke; Yamanashi, Kenji; Chemical and pharmaceutical bulletin; vol. 50; nb. 10; (2002); p. 1362 - 1366 View in Reaxys

O S

O

O

OH NH

O O

O

HO

H 2N

Rx-ID: 14547651 View in Reaxys 51/109 Yield

Conditions & References Reaction Steps: 2 1: 72.4 percent / NaI; Zn / dimethylformamide / 10 h / 120 °C 2: 80.3 percent / HCl / 10 h / Heating With hydrogenchloride, sodium iodide, zinc in N,N-dimethyl-formamide Shiraiwa, Tadashi; Suzuki, Masahiro; Sakai, Yoshio; Nagasawa, Hisashi; Takatani, Kazuhiro; Noshi, Daisuke; Yamanashi, Kenji; Chemical and pharmaceutical bulletin; vol. 50; nb. 10; (2002); p. 1362 - 1366 View in Reaxys O

O

O NH 2

HO

H 2N

Rx-ID: 14657140 View in Reaxys 52/109 Yield

Conditions & References Reaction Steps: 2 1.1: CH2Cl2 / 5 h / Heating 2.1: lithium diisopropylamide; TiCl4*2THF; (2R,3R)-1,4-dimethoxy-1,1,4,4,-tetraphenylbutane-2,3-diol / tetrahydrofuran / 0.5 h / -60 °C 2.2: tetrahydrofuran / 12 h / -15 °C 2.3: hydrochloric acid / tetrahydrofuran; H2O / 10 h / Heating With tetrachlorobis(tetrahydrofuran)titanium(IV), (2R,3R)-1,4-dimethoxy-1,1,4,4-tetraphenyl-2,3-butandiol, lithium diisopropyl amide in tetrahydrofuran, dichloromethane Hu, Ai-Guo; Zhang, Ling-Yun; Wang, Shan-Wei; Wang, Ji-Tao; Synthetic Communications; vol. 32; nb. 14; (2002); p. 2143 - 2147 View in Reaxys

O

O

Br

N

E

OH NH 2

O

O HO

H 2N

Rx-ID: 8520466 View in Reaxys 53/109 Yield 40 %

Conditions & References Stage 1: With sodium hydroxide, (R,R)-TADDOL in toluene, Time= 12h, T= 15 - 20 °C , Alkylation, benzylation Stage 2: With hydrogenchloride in water, toluene, Heating, Hydrolysis Belokon'; Kochetkov; Churkina; Ikonnikov; Chesnokov; Larionov; Kagan; Russian Chemical Bulletin; vol. 48; nb. 5; (1999); p. 917 - 923 View in Reaxys Stage 1: With sodium hydroxide, (R,R)-TADDOL in toluene, Time= 12h, T= 15 - 20 °C , Alkylation, benzylation

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Stage 2: With hydrogenchloride in water, toluene, Heating, Hydrolysis, Title compound not separated from byproducts Belokon'; Kochetkov; Churkina; Ikonnikov; Chesnokov; Larionov; Kagan; Russian Chemical Bulletin; vol. 48; nb. 5; (1999); p. 917 - 923 View in Reaxys Stage 1: With sodium hydroxide, (S)-3,3'-bis[(diethylamino)methyl]-2,2'-dihydroxy-1,1'-binaphthalene in toluene, Time= 40h, T= 20 °C Stage 2: With hydrogenchloride in water, Time= 1h, Heating Stage 3: With methyloxirane in ethanol, Time= 0.5h, Heating, Title compound not separated from byproducts Casas, Jesus; Najera, Carmen; Sansano, Jose M.; Gonzalez, Jose; Saa, Jose M.; Vega, Manuel; Tetrahedron Asymmetry; vol. 12; nb. 5; (2001); p. 699 - 702 View in Reaxys

O O

O

N

HO

H 2N

Rx-ID: 8636027 View in Reaxys 54/109 Yield

Conditions & References

62 %

Stage 1: With sodium hydroxide in methanol, T= 20 °C , Hydrolysis Stage 2: With hydrogen, palladium on activated charcoal in ethanol, Time= 36h, T= 40 °C , p= 30402Torr , Hydrogenation, Further stages.

Ma, Dawei; Ding, Ke; Organic Letters; vol. 2; nb. 16; (2000); p. 2515 - 2517 View in Reaxys Reaction Steps: 2 1: aq. NaOH / methanol / 20 °C 2: H2 / Pd/C / ethanol / 36 h / 40 °C / 30400 Torr With sodium hydroxide, hydrogen, palladium on activated charcoal in methanol, ethanol Ding, Ke; Ma, Dawei; Tetrahedron; vol. 57; nb. 30; (2001); p. 6361 - 6366 View in Reaxys

O

O Cl O

H

OH NH 2

O HO

H 2N

H 2N

Rx-ID: 8786317 View in Reaxys 55/109 Yield

Conditions & References With hydrogenchloride, Heating Belokon, Yuri N; North, Michael; Churkina, Tatiana D; Ikonnikov, Nikolai S; Maleev, Victor I; Tetrahedron; vol.

57; nb. 13; (2001); p. 2491 - 2498 View in Reaxys

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HO O

OH

O

N

HO

H 2N

Rx-ID: 8849078 View in Reaxys 56/109 Yield

Conditions & References With hydrogen, palladium on activated charcoal in ethanol, Time= 36h, T= 40 °C , p= 30400Torr Ding, Ke; Ma, Dawei; Tetrahedron; vol. 57; nb. 30; (2001); p. 6361 - 6366 View in Reaxys

O

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

Br

HO

H 2N

Rx-ID: 15388436 View in Reaxys 57/109 Yield

Conditions & References Reaction Steps: 3 1.1: NaHMDS / tetrahydrofuran; 1,2-dimethoxy-ethane / 1.25 h / -78 °C 1.2: 90 percent / tetrahydrofuran; 1,2-dimethoxy-ethane / 8 h / -78 °C 2.1: aq. NaOH / methanol / 20 °C 3.1: H2 / Pd/C / ethanol / 36 h / 40 °C / 30400 Torr With sodium hydroxide, hydrogen, sodium hexamethyldisilazane, palladium on activated charcoal in tetrahydrofuran, methanol, 1,2-dimethoxyethane, ethanol Ding, Ke; Ma, Dawei; Tetrahedron; vol. 57; nb. 30; (2001); p. 6361 - 6366 View in Reaxys Reaction Steps: 2 1.1: NaHMDS / 1,2-dimethoxy-ethane; tetrahydrofuran / -78 °C 1.2: 90 percent / 1,2-dimethoxy-ethane; tetrahydrofuran 2.1: aq. NaOH / methanol / 20 °C 2.2: 62 percent / H2 / Pd/C / ethanol / 36 h / 40 °C / 30402 Torr With sodium hydroxide, sodium hexamethyldisilazane in tetrahydrofuran, methanol, 1,2-dimethoxyethane, 1.1: Metallation / 1.2: Alkylation / 2.1: Hydrolysis / 2.2: Hydrogenation Ma, Dawei; Ding, Ke; Organic Letters; vol. 2; nb. 16; (2000); p. 2515 - 2517 View in Reaxys

O

O N

O

O

N

HO

H 2N

Rx-ID: 4965422 View in Reaxys 58/109 Yield 72 %

Conditions & References With hydrogenchloride, Time= 36h, T= 150 °C Abellan, Tomas; Najera, Carmen; Sansano, Jose M.; Tetrahedron Asymmetry; vol. 9; nb. 13; (1998); p. 2211 2214 View in Reaxys

72 %

With hydrogenchloride, Time= 72h, T= 150 °C , Hydrolysis

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Najera, Carmen; Abellan, Tomas; Sansano, Jose M.; European Journal of Organic Chemistry; nb. 15; (2000); p.

2809 - 2820 View in Reaxys

O HO

O

H N

N H

O

O

O

N H

HO

O

H 2N

OH

Rx-ID: 8592924 View in Reaxys 59/109 Yield

Conditions & References With carboxypeptidase A in water, T= 25 °C , pH= 7.5, Hydrolysis, Enzyme kinetics Lee, Mijoon; Kim, Dong H.; Bioorganic and Medicinal Chemistry; vol. 8; nb. 4; (2000); p. 815 - 823 View in Reaxys

O O

OH NH 2

N O

Br

O HO

H 2N

Rx-ID: 8688344 View in Reaxys 60/109 Yield

Conditions & References Stage 1: With sodium hydride, (R,R)-TADDOL in toluene, Time= 12h, T= 15 - 20 °C , Substitution Stage 2: With hydrogenchloride in water, Time= 0.25h, Hydrolysis, Further stages. Title compound not separated from byproducts.

Belokon, Yuri N.; Kochetkov, Konstantin A.; Churkina, Tatiana D.; Ikonnikov, Nikolai S.; Chesnokov, Alexey A.; Larionov, Oleg V.; Singh, Ishwar; Parmar, Virinder S.; Vyskocil, Stepan; Kagan, Henri B.; Journal of Organic Chemistry; vol. 65; nb. 21; (2000); p. 7041 - 7048 View in Reaxys

O

O

Br

N

OH NH 2

O

O HO

H 2N

Rx-ID: 8688448 View in Reaxys 61/109 Yield 40 %

Conditions & References Stage 1: With sodium hydroxide, (R,R)-TADDOL in toluene, Time= 12h, T= 15 - 20 °C , Substitution Stage 2: With hydrogenchloride in water, Time= 0.25h, Hydrolysis Belokon, Yuri N.; Kochetkov, Konstantin A.; Churkina, Tatiana D.; Ikonnikov, Nikolai S.; Chesnokov, Alexey A.; Larionov, Oleg V.; Singh, Ishwar; Parmar, Virinder S.; Vyskocil, Stepan; Kagan, Henri B.; Journal of Organic Chemistry; vol. 65; nb. 21; (2000); p. 7041 - 7048 View in Reaxys Stage 1: With sodium hydroxide, (R,R)-TADDOL in toluene, Time= 12h, T= 15 - 20 °C , Substitution Stage 2: With hydrogenchloride in water, Time= 0.25h, Hydrolysis, Title compound not separated from byproducts Belokon, Yuri N.; Kochetkov, Konstantin A.; Churkina, Tatiana D.; Ikonnikov, Nikolai S.; Chesnokov, Alexey A.; Larionov, Oleg V.; Singh, Ishwar; Parmar, Virinder S.; Vyskocil, Stepan; Kagan, Henri B.; Journal of Organic Chemistry; vol. 65; nb. 21; (2000); p. 7041 - 7048 View in Reaxys

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O O

NH 2

N O

Br

OH

O HO

F

H 2N

Rx-ID: 8688461 View in Reaxys 62/109 Yield

Conditions & References Stage 1: With sodium hydroxide, (R,R)-TADDOL in toluene, Time= 12h, T= 15 - 20 °C , Substitution Stage 2: With hydrogenchloride in water, Time= 0.25h, Hydrolysis, Further stages. Title compound not separated from byproducts.

Belokon, Yuri N.; Kochetkov, Konstantin A.; Churkina, Tatiana D.; Ikonnikov, Nikolai S.; Chesnokov, Alexey A.; Larionov, Oleg V.; Singh, Ishwar; Parmar, Virinder S.; Vyskocil, Stepan; Kagan, Henri B.; Journal of Organic Chemistry; vol. 65; nb. 21; (2000); p. 7041 - 7048 View in Reaxys

O

O

NH 2

N O

Br

OH

O HO

Cl

H 2N

Rx-ID: 8688462 View in Reaxys 63/109 Yield

Conditions & References Stage 1: With sodium hydroxide, (R,R)-TADDOL in toluene, Time= 12h, T= 15 - 20 °C , Substitution Stage 2: With hydrogenchloride in water, Time= 0.25h, Hydrolysis, Further stages. Title compound not separated from byproducts.

Belokon, Yuri N.; Kochetkov, Konstantin A.; Churkina, Tatiana D.; Ikonnikov, Nikolai S.; Chesnokov, Alexey A.; Larionov, Oleg V.; Singh, Ishwar; Parmar, Virinder S.; Vyskocil, Stepan; Kagan, Henri B.; Journal of Organic Chemistry; vol. 65; nb. 21; (2000); p. 7041 - 7048 View in Reaxys

O O

O

N

HO

H 2N

Rx-ID: 4700932 View in Reaxys 64/109 Yield 80 %

Conditions & References With hydrogenchloride, methyloxirane, 1.) 150 deg C, 2.) EtOH, heating Chinchilla; Falvello; Galindo; Najera; Angewandte Chemie - International Edition in English; vol. 36; nb. 9; (1997); p. 995 - 997 View in Reaxys

80 %

With hydrogenchloride, water, Time= 24h, T= 150 °C Chinchilla, Rafael; Galindo, Nuria; Najera, Carmen; Synthesis; nb. 4; (1999); p. 704 - 717 View in Reaxys

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O N O

HO

O HO

O O

O

H 2N

HN

O

HO

O

Rx-ID: 5234371 View in Reaxys 65/109 Yield 52 %, 35 %

Conditions & References With sodium hydroxide in tetrahydrofuran, Time= 192h, Hydrolysis Achatz, Oliver; Grandl, Andrea; Wanner, Klaus Theodor; European Journal of Organic Chemistry; nb. 8; (1999); p. 1967 - 1978 View in Reaxys

O O

N

NH 2

E

O

Br

OH

O HO

F

H 2N

Rx-ID: 8520467 View in Reaxys 66/109 Yield

Conditions & References Stage 1: With sodium hydroxide, (R,R)-TADDOL in toluene, Time= 12h, T= 15 - 20 °C , Alkylation, benzylation Stage 2: With hydrogenchloride in water, toluene, Heating, Hydrolysis, Title compound not separated from byproducts Belokon'; Kochetkov; Churkina; Ikonnikov; Chesnokov; Larionov; Kagan; Russian Chemical Bulletin; vol. 48; nb. 5; (1999); p. 917 - 923 View in Reaxys

O

O

N

NH 2

E

O

Br

OH

O HO

Cl

H 2N

Rx-ID: 8520468 View in Reaxys 67/109 Yield

Conditions & References Stage 1: With sodium hydroxide, (R,R)-TADDOL in toluene, Time= 12h, T= 15 - 20 °C , Alkylation, benzylation Stage 2: With hydrogenchloride in water, toluene, Heating, Hydrolysis, Title compound not separated from byproducts Belokon'; Kochetkov; Churkina; Ikonnikov; Chesnokov; Larionov; Kagan; Russian Chemical Bulletin; vol. 48; nb. 5; (1999); p. 917 - 923 View in Reaxys

O N O

O HO

O O

H 2N

Rx-ID: 16331130 View in Reaxys 68/109 Yield

Conditions & References Reaction Steps: 2

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1.1: sBuLi / 1,2-dimethoxy-ethane; heptane; cyclohexane / 0.25 h / -55 °C 1.2: 78 percent / 1,2-dimethoxy-ethane; heptane; cyclohexane / 16 h / -55 °C 2.1: 52 percent / aq. NaOH / tetrahydrofuran / 192 h With sodium hydroxide, sec.-butyllithium in tetrahydrofuran, 1,2-dimethoxyethane, n-heptane, cyclohexane, 1.1: Metallation / 1.2: Methylation / 2.1: Hydrolysis Achatz, Oliver; Grandl, Andrea; Wanner, Klaus Theodor; European Journal of Organic Chemistry; nb. 8; (1999); p. 1967 - 1978 View in Reaxys

O

t-BuOCOCH2-X

Br

HO

H 2N

Rx-ID: 16437437 View in Reaxys 69/109 Yield

Conditions & References Reaction Steps: 2 1: 75 percent / TBAB, K2CO3 / acetonitrile / 8 h / Ambient temperature 2: 80 percent / HCl, H2O / 24 h / 150 °C With hydrogenchloride, tetrabutylammomium bromide, water, potassium carbonate in acetonitrile Chinchilla, Rafael; Galindo, Nuria; Najera, Carmen; Synthesis; nb. 4; (1999); p. 704 - 717 View in Reaxys

O

(Bu4N)2[Zn(α-C3S5)2]

Cl

HO

H 2N

Rx-ID: 16439616 View in Reaxys 70/109 Yield

Conditions & References Reaction Steps: 2 1: 45 percent / 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine, LiI / various solvent(s) / 1 h / Ambient temperature 2: 80 percent / HCl, H2O / 24 h / 150 °C With hydrogenchloride, water, 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine, lithium iodide in various solvent(s) Chinchilla, Rafael; Galindo, Nuria; Najera, Carmen; Synthesis; nb. 4; (1999); p. 704 - 717 View in Reaxys

H 2N O

H 2N

O HO

H 2N

Rx-ID: 2203447 View in Reaxys 71/109 Yield

Conditions & References T= 37 °C , Mycobacterium neoaurum ATCC 25795, pH 8-8.5, Yield given Kaptein; Boesten; Broxterman; Peters; Schoemaker; Kamphuis; Tetrahedron Asymmetry; vol. 4; nb. 6; (1993); p. 1113 - 1116 View in Reaxys With potassium phosphate buffer, Mycobacterium neoaurum ATCC 25795, Time= 1h, T= 30 °C Patel; Banerjee; Chu; Brozozowski; Nanduri; Szarka; JAOCS, Journal of the American Oil Chemists' Society; vol. 75; nb. 11; (1998); p. 1473 - 1482 View in Reaxys

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

Br

O HO

H 2N

Rx-ID: 16787912 View in Reaxys 72/109 Yield

Conditions & References Reaction Steps: 2 1: 81 percent / K2CO3, tertra-n-butylammonium bromide / acetonitrile / 5 h / Ambient temperature 2: 72 percent / 6 N aq. HCl / 36 h / 150 °C With hydrogenchloride, tetrabutylammomium bromide, potassium carbonate in acetonitrile Abellan, Tomas; Najera, Carmen; Sansano, Jose M.; Tetrahedron Asymmetry; vol. 9; nb. 13; (1998); p. 2211 2214 View in Reaxys Reaction Steps: 2 1: 75 percent / K2CO3, TBAB / acetonitrile / 8 h / Ambient temperature 2: 80 percent / 6 N aq. HCl, propylene oxide / 1.) 150 deg C, 2.) EtOH, heating With hydrogenchloride, tetrabutylammomium bromide, potassium carbonate, methyloxirane in acetonitrile Chinchilla; Falvello; Galindo; Najera; Angewandte Chemie - International Edition in English; vol. 36; nb. 9; (1997); p. 995 - 997 View in Reaxys

O

O

O

N

HO

H 2N

Rx-ID: 4540083 View in Reaxys 73/109 Yield

Conditions & References With water, chymotrypsin in acetonitrile, Time= 200h, Yield given Parmar, Virinder S.; Singh, Amarjit; Bisht, Kirpal S.; Kumar, Naresh; Belokon; Kochetkov; Ikonnikov; Orlova; Tararov; Saveleva; Journal of Organic Chemistry; vol. 61; nb. 4; (1996); p. 1223 - 1226 View in Reaxys

H 2N O

H 2N

O HO

H 2N

H 2N O

H 2N

Rx-ID: 2203448 View in Reaxys 74/109 Yield 81 %, 66 %

Conditions & References in water, T= 37 °C , Ochrobactrum anthropi NCIMB 40321, pH 5.6 Kaptein, Bernard; Monaco, Vania; Broxterman, Quirinus B.; Schoemaker, Hans E.; Kamphuis, Johan; Recueil des Travaux Chimiques des Pays-Bas; vol. 114; nb. 4-5; (1995); p. 231 - 238 View in Reaxys With water, Time= 72h, T= 37 °C , aminopeptidase from Mycobacterium neoaurum ATCC 25795 Kruizinga, Wim H.; Bolster, John; Kellogg, Richard M.; Kamphuis, Johan; Boesten, Wilhelmus H. J.; et al.; Journal of Organic Chemistry; vol. 53; nb. 8; (1988); p. 1826 - 1827 View in Reaxys

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O

OH

O O

NH 2

N H

O

O HO

H 2N

Rx-ID: 4109122 View in Reaxys 75/109 Yield

Conditions & References With hydrogenchloride, Time= 7h, T= 120 °C , Yield given. Yields of byproduct given. Title compound not separated from byproducts Berkowitz, David B.; Smith, Marianne K.; Journal of Organic Chemistry; vol. 60; nb. 5; (1995); p. 1233 - 1238 View in Reaxys

O

O NH

HO

O

O

H 2N

Rx-ID: 4200633 View in Reaxys 76/109 Yield

Conditions & References With hydrogenchloride in 1,4-dioxane, Time= 12h, T= 100 °C Obrecht; Bohdal; Broger; Bur; Lehmann; Ruffieux; Schonholzer; Spiegler; Muller; Helvetica Chimica Acta; vol.

78; nb. 3; (1995); p. 563 - 580 View in Reaxys

O

O

O O

O

HO

NH

H 2N

O

Rx-ID: 4282564 View in Reaxys 77/109 Yield 96 %

Conditions & References With hydrogen, palladium on activated charcoal in methanol, Time= 2h, T= 25 °C Jung, Michael E.; D'Amico, Derin C.; Journal of the American Chemical Society; vol. 117; nb. 28; (1995); p. 7379 7388 View in Reaxys

O

O

O

O HO

H 2N

Rx-ID: 18029012 View in Reaxys 78/109 Yield

Conditions & References Reaction Steps: 5 1: 98 percent / 2-methyl2-butene, NaClO2, NaH2PO4 / 2-methyl-propan-2-ol; H2O / 1 h / 25 °C 2: 1.) carbonyldiimidazole, 2.) NH3 / 1.) CH2Cl2, 25 deg C, 1.5 h, 2.) CH2Cl2, 25 deg C, overnight 3: 91 percent / lead tetraacetate / dimethylformamide / 1 h / 100 - 110 °C 4: 1.) ozone, 2.) dimethyl sulfide / 1.) CH2Cl2, -78 deg C, 15 min, 2.) CH2Cl2, 25 deg C, overnight 5: 96 percent / H2 / 9percent Pd/C / methanol / 2 h / 25 °C

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With lead(IV) acetate, sodium chlorite, sodium dihydrogenphosphate, 2-methyl-but-2-ene, dimethylsulfide, ammonia, hydrogen, ozone, 1,1'-carbonyldiimidazole, palladium on activated charcoal in methanol, water, N,N-dimethyl-formamide, tert-butyl alcohol Jung, Michael E.; D'Amico, Derin C.; Journal of the American Chemical Society; vol. 117; nb. 28; (1995); p. 7379 7388 View in Reaxys

O O

HO

O

O HO

H 2N

Rx-ID: 18031030 View in Reaxys 79/109 Yield

Conditions & References Reaction Steps: 4 1: 1.) carbonyldiimidazole, 2.) NH3 / 1.) CH2Cl2, 25 deg C, 1.5 h, 2.) CH2Cl2, 25 deg C, overnight 2: 91 percent / lead tetraacetate / dimethylformamide / 1 h / 100 - 110 °C 3: 1.) ozone, 2.) dimethyl sulfide / 1.) CH2Cl2, -78 deg C, 15 min, 2.) CH2Cl2, 25 deg C, overnight 4: 96 percent / H2 / 9percent Pd/C / methanol / 2 h / 25 °C With lead(IV) acetate, dimethylsulfide, ammonia, hydrogen, ozone, 1,1'-carbonyldiimidazole, palladium on activated charcoal in methanol, N,N-dimethyl-formamide Jung, Michael E.; D'Amico, Derin C.; Journal of the American Chemical Society; vol. 117; nb. 28; (1995); p. 7379 7388 View in Reaxys

NH 2 O

O

O

O HO

H 2N

Rx-ID: 18031033 View in Reaxys 80/109 Yield

Conditions & References Reaction Steps: 3 1: 91 percent / lead tetraacetate / dimethylformamide / 1 h / 100 - 110 °C 2: 1.) ozone, 2.) dimethyl sulfide / 1.) CH2Cl2, -78 deg C, 15 min, 2.) CH2Cl2, 25 deg C, overnight 3: 96 percent / H2 / 9percent Pd/C / methanol / 2 h / 25 °C With lead(IV) acetate, dimethylsulfide, hydrogen, ozone, palladium on activated charcoal in methanol, N,N-dimethylformamide Jung, Michael E.; D'Amico, Derin C.; Journal of the American Chemical Society; vol. 117; nb. 28; (1995); p. 7379 7388 View in Reaxys

O O O

O O

NH

HO

H 2N

Rx-ID: 18038217 View in Reaxys 81/109 Yield

Conditions & References Reaction Steps: 2 1: 1.) ozone, 2.) dimethyl sulfide / 1.) CH2Cl2, -78 deg C, 15 min, 2.) CH2Cl2, 25 deg C, overnight 2: 96 percent / H2 / 9percent Pd/C / methanol / 2 h / 25 °C With dimethylsulfide, hydrogen, ozone, palladium on activated charcoal in methanol

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Jung, Michael E.; D'Amico, Derin C.; Journal of the American Chemical Society; vol. 117; nb. 28; (1995); p. 7379 7388 View in Reaxys

O O

O HO

H 2N

O O

H 2N

H 2N

Rx-ID: 2204967 View in Reaxys 82/109 Yield

Conditions & References

37.4 %

in various solvent(s), Time= 6h, Ambient temperature, Candida lypolythica esterase Yee, Christopher; Blythe, Todd A.; McNabb, Thomas J.; Walts, Alan E.; Journal of Organic Chemistry; vol. 57; nb. 13; (1992); p. 3525 - 3527 View in Reaxys

37.4 %

in various solvent(s), Time= 6h, Ambient temperature, Candida lypolythica esterase, Yields of byproduct given Yee, Christopher; Blythe, Todd A.; McNabb, Thomas J.; Walts, Alan E.; Journal of Organic Chemistry; vol. 57; nb. 13; (1992); p. 3525 - 3527 View in Reaxys

O

O

O O

H 2N

HO

O

H 2N

H 2N

Rx-ID: 3107715 View in Reaxys 83/109 Yield

Conditions & References in various solvent(s), Ambient temperature, Candida lipolythica lipase (active component: Candida lypolythica esterase), Yield given. Yields of byproduct given Yee, Christopher; Blythe, Todd A.; McNabb, Thomas J.; Walts, Alan E.; Journal of Organic Chemistry; vol. 57; nb. 13; (1992); p. 3525 - 3527 View in Reaxys

O HO

H 2N

Rx-ID: 7789536 View in Reaxys 84/109 Yield 95%

Conditions & References 3.b : b. b.

(2S)-2-Amino-2-Methyl-3-Phenylpropanoic Acid Following the procedure described in example 1c, hydrolysis of the resultant compound from example 3a (190 mg, 0.614 mmol) with LiOH (1.03 g, 24.6 mmol) in aqueous dioxane (85 ml) afforded the title compound as a colorless powder (105 mg, 95percent). [α]D =-19.1° (c=1.04, H2 O), Lit [α]D =-20.7° (c=0.805, H2 O) for S isomer; MS(FAB): 180(M+H)+; NMR(D2 O) 1.57(s, 3H), 3.01(d, 1H, J=14Hz), 3.31(d, 1H, J=14Hz), 7.26-7.45(m, 5H).

C NMR(D2 O): 22.92, 43.21, 62.69, 128.35, 129.501, 130.54, 134.77, 176.65.

13

Patent; Abbott Laboratories; US5153358; (1992); (A1) English View in Reaxys Patent; BASF AG; DE2658942; (1978); ; vol. 89; nb. 179988 View in Reaxys Patent; BASF AG; DE2658941; (1978); ; vol. 90; nb. 23701 View in Reaxys Kolb; Barth; Tetrahedron Letters; (1979); p. 2999,3000,3001 View in Reaxys

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Iwasaki; Harada; Journal of the Chemical Society. Perkin transactions 1; vol. 15; (1977); p. 1730 - 1733 View in Reaxys Iwasaki; Harada; Journal of the Chemical Society, Chemical Communications; (1974); p. 338 View in Reaxys

O O

HN

O

O

O

HO

H 2N

Rx-ID: 2525168 View in Reaxys 85/109 Yield

Conditions & References With potassium hydroxide, 18-crown-6 ether, Time= 24h, Heating Ihara, Masataka; Takahashi, Masanobu; Taniguchi, Nobuaki; Yasui, Ken; Niitsuma, Hiroko; Fukumoto, Keiichiro; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); nb.

3; (1991); p. 525 - 535 View in Reaxys

O O O

N

O

O

HO

H 2N

Rx-ID: 2802539 View in Reaxys 86/109 Yield

Conditions & References

93 %

With hydrogen, palladium dichloride in tetrahydrofuran, ethanol, Time= 48h, p= 2585.7Torr Williams; Im; Journal of the American Chemical Society; vol. 113; nb. 24; (1991); p. 9276 - 9286 View in Reaxys

O O

HO

H 2N

O O OH

Rx-ID: 21658368 View in Reaxys 87/109 Yield

Conditions & References Reaction Steps: 2 1: 1) diphenylphosphoryl azide, NEt3 / 1) benzene, reflux, 2 h, 2) reflux, 20 h 2: KOH, 18-crown-6 / 24 h / Heating With potassium hydroxide, 18-crown-6 ether, diphenylphosphoranyl azide, triethylamine Ihara, Masataka; Takahashi, Masanobu; Taniguchi, Nobuaki; Yasui, Ken; Niitsuma, Hiroko; Fukumoto, Keiichiro; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); nb.

3; (1991); p. 525 - 535 View in Reaxys

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O O

HO

OH O

H 2N

O

Rx-ID: 21658545 View in Reaxys 88/109 Yield

Conditions & References Reaction Steps: 3 1: 1) LDA / 1) THF, -78 deg C, 45 min, 2) -78 deg C, 2 h 2: 1) diphenylphosphoryl azide, NEt3 / 1) benzene, reflux, 2 h, 2) reflux, 20 h 3: KOH, 18-crown-6 / 24 h / Heating With potassium hydroxide, 18-crown-6 ether, diphenylphosphoranyl azide, triethylamine, lithium diisopropyl amide Ihara, Masataka; Takahashi, Masanobu; Taniguchi, Nobuaki; Yasui, Ken; Niitsuma, Hiroko; Fukumoto, Keiichiro; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); nb.

3; (1991); p. 525 - 535 View in Reaxys

O

OH

O O

NH 2 N

O

O HO

O

H 2N

H

Rx-ID: 2459937 View in Reaxys 89/109 Yield

Conditions & References With lithium hydroxide in 1,4-dioxane, water, Time= 0.333333h, T= 25 °C , Yield given. Yields of byproduct given.

Title compound not separated from byproducts Zydowsky; De Lara; Spanton; Journal of Organic Chemistry; vol. 55; nb. 20; (1990); p. 5437 - 5439 View in Reaxys

O O

O

N

O O

H

HO

H 2N

Rx-ID: 21775851 View in Reaxys 90/109 Yield

Conditions & References Reaction Steps: 2 1: 1) LiHMDS, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone / 1) THF, -78 deg C, 15 min 2) -78 to -30 deg C, 2h 2: LiOH / dioxane; H2O / 0.33 h / 25 °C With 1,3 -dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, lithium hydroxide, lithium hexamethyldisilazane in 1,4-dioxane, water Zydowsky; De Lara; Spanton; Journal of Organic Chemistry; vol. 55; nb. 20; (1990); p. 5437 - 5439 View in Reaxys

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O

O

HO

OH NH 2

HN

O

O HO

O

OH N H

HN HO

O

O

Cl

O

H 2N

Cl

Cl

Rx-ID: 3196645 View in Reaxys 91/109 Yield

Conditions & References

43 %

With potassium hydroxide, porcine kidney acylase I, pH 7.5-8.0 Chenault, H. Keith; Dahmer, Juergen; Whitesides, George M.; Journal of the American Chemical Society; vol.

111; nb. 16; (1989); p. 6354 - 6364 View in Reaxys

43 %

With potassium hydroxide, porcine kidney acylase I, pH 7.5-8.0 Chenault, H. Keith; Dahmer, Juergen; Whitesides, George M.; Journal of the American Chemical Society; vol.

111; nb. 16; (1989); p. 6354 - 6364 View in Reaxys With potassium hydroxide, porcine kidney acylase I, pH 7.5-8.0, Yield given. Yields of byproduct given Chenault, H. Keith; Dahmer, Juergen; Whitesides, George M.; Journal of the American Chemical Society; vol.

111; nb. 16; (1989); p. 6354 - 6364 View in Reaxys

O

O

HO

HO

O

HN

HN HO

O

O

H 2N

Cl

Cl

Rx-ID: 3196646 View in Reaxys 92/109 Yield

Conditions & References With potassium hydroxide, potassium phosphate buffer, porcine kidney acylase I, T= 40 °C , relative initial rate of hydrolysis, also with Aspergillus acylase I as a catalyst; with or without CoCl2 Chenault, H. Keith; Dahmer, Juergen; Whitesides, George M.; Journal of the American Chemical Society; vol.

111; nb. 16; (1989); p. 6354 - 6364 View in Reaxys

O

H 2N Br

O

OH NH 2

OH

O HO

H 2N

Rx-ID: 2394235 View in Reaxys 93/109 Yield

Conditions & References Yield given. Multistep reaction. Yields of byproduct given Belokon, Yuri N.; Bakhmutov, Vladimir I.; Chernoglazova, Nina I.; Kochetkov, Konstantin A.; Vitt, Sergei V.; et al.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1988); p. 305 - 312 View in Reaxys Yield given. Multistep reaction Belokon', Yuri N.; Chernoglazova, Nina I.; Kochetkov, Constantin A.; Garbalinskaya, Natalia S.; Belikov, Vasili M.; Journal of the Chemical Society, Chemical Communications; nb. 3; (1985); p. 171 - 172 View in Reaxys

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O

OH

O NH 2

O

O

HN

HO

O

H 2N

Rx-ID: 2660087 View in Reaxys 94/109 Yield

Conditions & References With hydrogen cation, methyloxirane, 2.) ethanol, Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Georg, Gunda I.; Guan, Xiangming; Kant, Joydeep; Tetrahedron Letters; vol. 29; nb. 4; (1988); p. 403 - 406 View in Reaxys

O

O O

HO

H 2N

O

Rx-ID: 21489980 View in Reaxys 95/109 Yield

Conditions & References Reaction Steps: 2 1: 95 percent / methanesulfonic acid, sodium azide / CHCl3 / 1 h / Heating 2: 1.) H(+); 2.) propylene oxide / 2.) ethanol With sodium azide, methanesulfonic acid, hydrogen cation, methyloxirane in chloroform Georg, Gunda I.; Guan, Xiangming; Kant, Joydeep; Tetrahedron Letters; vol. 29; nb. 4; (1988); p. 403 - 406 View in Reaxys

N O

O

O

O–

Ni 2+

N

HO N–

N

HN

H 2N

O

O

Rx-ID: 3287038 View in Reaxys 96/109 Yield

Conditions & References

80 %

With hydrogenchloride in ethanol, Time= 0.333333h, Heating Belokon', Yu. N.; Chernoglazova, N. I.; Bakhmutov, V. I.; Garbalinskaya, N. S.; Belikov, V. M.; Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation); vol. 36; nb. 12; (1987); p.

2595 - 2601; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; nb. 12; (1987); p. 2798 - 2804 View in Reaxys

O

O

O N O

HO

H 2N

Rx-ID: 2835408 View in Reaxys 97/109 Yield

Conditions & References With hydrogenchloride, Time= 3h, Heating, Yield given

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Bjoerkling, Fredrik; Boutelje, John; Gatenbeck, Sten; Hult, Karl; Norin, Torbjoern; Szmulik, Peter; Tetrahedron; vol. 41; nb. 7; (1985); p. 1347 - 1352 View in Reaxys

O O

O O HO

N N

H 2N

N

Rx-ID: 20844954 View in Reaxys 98/109 Yield

Conditions & References Reaction Steps: 2 1: toluene / 100 °C 2: 20percent aq HCl / 3 h / Heating With hydrogenchloride in toluene Bjoerkling, Fredrik; Boutelje, John; Gatenbeck, Sten; Hult, Karl; Norin, Torbjoern; Szmulik, Peter; Tetrahedron; vol. 41; nb. 7; (1985); p. 1347 - 1352 View in Reaxys

O

O

O O

HO OH

H 2N

Rx-ID: 20855585 View in Reaxys 99/109 Yield

Conditions & References Reaction Steps: 3 1: 1.) Et3N, ethyl chloroformate; 2.) NaN3 / 1.) acetone, 0 deg C, 30 min; 2.) H2O, 0 deg C, 1 h 2: toluene / 100 °C 3: 20percent aq HCl / 3 h / Heating With hydrogenchloride, sodium azide, chloroformic acid ethyl ester, triethylamine in toluene Bjoerkling, Fredrik; Boutelje, John; Gatenbeck, Sten; Hult, Karl; Norin, Torbjoern; Szmulik, Peter; Tetrahedron; vol. 41; nb. 7; (1985); p. 1347 - 1352 View in Reaxys

O

O

O NH O

HO

H 2N

OH

Rx-ID: 2669964 View in Reaxys 100/109 Yield

Conditions & References With hydrogen, palladium on activated charcoal in methanol, Time= 2h, p= 2068.6Torr , Ambient temperature Karady, Sandor; Amato, Joseph S.; Weinstock, Leonard M.; Tetrahedron Letters; vol. 25; nb. 39; (1984); p. 4337 - 4340 View in Reaxys

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O

OH

H

H N

O

O O

HO

H 2N

Rx-ID: 21520165 View in Reaxys 101/109 Yield

Conditions & References Reaction Steps: 4 1: p-toluolsulfonic acid / 1,1,1-trichloro-ethane / 18 h / Heating 2: 1) K-hexamethyldisilazide / 1) THF-toluene, -78 deg C, 5 min, 2) warming up to rt.

3: 1N NaOH / methanol / Ambient temperature 4: H2 / 10percent Pd/C / methanol / 2 h / 2068.6 Torr / Ambient temperature With sodium hydroxide, K-hexamethyldisilazide, hydrogen, toluene-4-sulfonic acid, palladium on activated charcoal in methanol, 1,1,1- trichloroethane Karady, Sandor; Amato, Joseph S.; Weinstock, Leonard M.; Tetrahedron Letters; vol. 25; nb. 39; (1984); p. 4337 - 4340 View in Reaxys

O O

O

HO

N

H 2N

O O

Rx-ID: 21538038 View in Reaxys 102/109 Yield

Conditions & References Reaction Steps: 2 1: 1N NaOH / methanol / Ambient temperature 2: H2 / 10percent Pd/C / methanol / 2 h / 2068.6 Torr / Ambient temperature With sodium hydroxide, hydrogen, palladium on activated charcoal in methanol Karady, Sandor; Amato, Joseph S.; Weinstock, Leonard M.; Tetrahedron Letters; vol. 25; nb. 39; (1984); p. 4337 - 4340 View in Reaxys

O O N

O

O O

HO

H 2N

Rx-ID: 21548062 View in Reaxys 103/109 Yield

Conditions & References Reaction Steps: 3 1: 1) K-hexamethyldisilazide / 1) THF-toluene, -78 deg C, 5 min, 2) warming up to rt.

2: 1N NaOH / methanol / Ambient temperature 3: H2 / 10percent Pd/C / methanol / 2 h / 2068.6 Torr / Ambient temperature With sodium hydroxide, K-hexamethyldisilazide, hydrogen, palladium on activated charcoal in methanol

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Karady, Sandor; Amato, Joseph S.; Weinstock, Leonard M.; Tetrahedron Letters; vol. 25; nb. 39; (1984); p. 4337 - 4340 View in Reaxys

O

O O

NH 2

O HO

H 2N

O

H 2N

Rx-ID: 2182790 View in Reaxys 104/109 Yield

Conditions & References

79 %

With α-chymotrypsin in water, Time= 35h, T= 37 °C , pH=5.0 Anantharamaiah, G. M.; Roeske, Roger W.; Tetrahedron Letters; vol. 23; nb. 33; (1982); p. 3335 - 3336 View in Reaxys With α-chymotrypsin in water, Time= 35h, T= 37 °C , pH=5.0 Anantharamaiah, G. M.; Roeske, Roger W.; Tetrahedron Letters; vol. 23; nb. 33; (1982); p. 3335 - 3336 View in Reaxys

O

-1

OH

F

H

NH 2

(v4)

O

NH 2

F

B FF

O+

Br

O HO

O

H 2N

Rx-ID: 2394246 View in Reaxys 105/109 Yield

Conditions & References Multistep reaction. Title compound not separated from byproducts Schoellkopf, Ulrich; Hartwig, Wolfgang; Groth, Ulrich; Westphalen, Karl-Otto; Liebigs Annalen der Chemie; nb.

4; (1981); p. 696 - 708 View in Reaxys

H N

O

O N

H

HO

H 2N

H 2N

Rx-ID: 3050717 View in Reaxys 106/109 Yield 67 %

Conditions & References With hydrogenchloride in methanol, water, 1) 24 h, reflux, 2) 24 h, reflux Schoellkopf, Ulrich; Hausberg, Hans-Heinrich; Segal, Marcos; Reiter, Udo; Hoppe, Inga; et al.; Liebigs Annalen der Chemie; nb. 3; (1981); p. 439 - 458 View in Reaxys

O

alcoholic potash Br

HO

H 2N

Rx-ID: 20635086 View in Reaxys 107/109

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Yield

Conditions & References Reaction Steps: 2 1: 1) butyllithium / 1) THF, hexane, -60 deg C, 2) THF, -60 deg C - room temperature 2: 67 percent / 1) gaseous HCl, 2) HCl / methanol; H2O / 1) 24 h, reflux, 2) 24 h, reflux With hydrogenchloride, n-butyllithium in methanol, water Schoellkopf, Ulrich; Hausberg, Hans-Heinrich; Segal, Marcos; Reiter, Udo; Hoppe, Inga; et al.; Liebigs Annalen der Chemie; nb. 3; (1981); p. 439 - 458 View in Reaxys

O

disodium-compound of 1,1,2,2-tetraphenyl-ethane Cl

HO

H 2N

Rx-ID: 20638983 View in Reaxys 108/109 Yield

Conditions & References Reaction Steps: 2 1: 50percent NaOH, benzyltriethylammoniumchloride / CH2Cl2 / 2 h / Ambient temperature 2: 67 percent / 1) gaseous HCl, 2) HCl / methanol; H2O / 1) 24 h, reflux, 2) 24 h, reflux With hydrogenchloride, sodium hydroxide, N-benzyl-N,N,N-triethylammonium chloride in methanol, dichloromethane, water Schoellkopf, Ulrich; Hausberg, Hans-Heinrich; Segal, Marcos; Reiter, Udo; Hoppe, Inga; et al.; Liebigs Annalen der Chemie; nb. 3; (1981); p. 439 - 458 View in Reaxys OH

O F

F

O

HN

F O

HO

H 2N

Rx-ID: 1137931 View in Reaxys 109/109 Yield

Conditions & References With sodium hydroxide, (enzymatic transformation) Turk; Panse; Marshall; The Journal of organic chemistry; vol. 40; nb. 7; (1975); p. 953 - 955 View in Reaxys

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