(1S,2R)-(+)-Norephedrine [CAS 37577-28-9; InChIKey DLNKOYKMWOXYQA-VXNVDRBHSA-N; Reaxys, All P

Query 1. Query

Query

Results

Date

RX.PXRN=2207678

63 reactions in Reaxys

2016-04-27 15h:50m:50s (EST)

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

1/24

2016-04-27 15:52:06

H

OH

H N

OH

H 2N H

Rx-ID: 23584495 View in Reaxys 1/63 Yield

Conditions & References

75%

27 : EXAMPLE 27 (1R, 2S)-1-phenyl-2-amino-1-propanol hydrochloride To a tetrahydrofuran solution (20 mL) of 1.319 g (5 mmol) of (1R,2S)-1-phenyl-2-[((1R)-phenylethyl)amino]-1-propanol synthesized in EXAMPLE 26, 500 mg of 10percent Pd/C was added, and the resulting solution was stirred under a hydrogen atmosphere at 3 atm at 35°C for 6 days. After the catalyst was filtered off, the solvent was distilled off under a reduced pressure to obtain (1R,2S)-1-phenyl-2-amino-1-propanol as a colorless oily substance (reaction yield: 75percent). To the substance, 40 mL of ethanol and 2 mL of 3 N hydrochloric acid were added, and the solvents were distilled off under a reduced pressure to obtain an oily substance. To this substance, 1.5 mL of ethanol and 10 mL of diisopropyl ether were added to precipitate crystals. White crystals of (1R,2S)-1-phenyl-2-amino-1propanol hydrochloride were obtained as a result (490.3 mg, isolation yield: 40percent). The optical purity and the diastereomer ratio thereof were determined by high-performance liquid chromatography (column: Daicel CROWNPAK CR(+), 4 .x. 150 mm, eluent: aqueous perchloric acid (pH = 1), flow: 0.5 mL/min, column temperature: 25°C, detector: UV 210 nm, retention time: (1R,2S)-isomer = 10.6 min, and (1S,2S)-isomer = 11.7 min, (1S,2R)-isomer = 14.1 min). The optical purity was 97.0percent e.e. The ratio, (1R,2S)-isomer/(1S,2S)-isomer was 92.9/7.1.1H-NMR (DMSO, 400 MHz/ppm): δ 0.98 (3H, d), 5.02 (1H, s), 5.98 (1H, s), 7.26-7.36 (5H, m), 8.17 (3H, brs) With hydrogen, palladium 10 on activated carbon in tetrahydrofuran, Time= 144h, T= 35 °C , p= 2280.15Torr , Product distribution / selectivity Patent; KANEKA CORPORATION; EP1512677; (2005); (A1) English View in Reaxys

H

OH

H 2N

O

H

N

N

N

Rx-ID: 41227742 View in Reaxys 2/63 Yield

Conditions & References (1R,2S)-2-amino-1-phenylpropan-1-ol hydrochloride (2): To a solution of azide 14 (0.20 g) in methanol was added 10percent Pd/C (30 mg). The resulting solution was stirred under hydrogen (1 atmosphere) for 12 h at room temperature until disappearance of the azido compound 14 as monitored by thin-layer chromatography (TLC). The reaction mixture was filtered through a celite pad to remove the catalyst and the filtrate was concentrated in vacuo to get norephedrine as colourless oil to which 3M methanolic HCl (3 mL) was added and stirred for 30 min. The reaction mixture was concentrated to give norephedrine hydrochloride as a colourless solid 2 (138 mg).

With palladium 10 on activated carbon, hydrogen in methanol, Time= 12h, T= 20 °C , p= 760.051Torr , enantioselective reaction Lalwani, Komal G.; Sudalai, Arumugam; Tetrahedron Letters; vol. 56; nb. 46; (2015); p. 6488 - 6490 View in Reaxys

H

OH

H 2N HO

H

H

N OH

Rx-ID: 438727 View in Reaxys 3/63

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

2/24

2016-04-27 15:52:06

Yield

Conditions & References With palladium, acetic acid, Hydrogenation Patent; I.G. Farbenind.; DE587586; (1930); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 20; p. 963 View in Reaxys 2 : Hydrogenation of L-Phenylacetylcarbinol-oxime with Novel Hydrogenation Catalyst 11 kg of L-Phenylacetylcarbinol-oxime as a solution in 200 L of water-methanol mixture (30:70) was mixed with 6 kg of sodium hydroxide. The solution was charged to a high-pressure autoclave equipped with heating jacket and agitator. 5.5 kg of the novel hydrogenation catalyst (prepared as e.g. example 1) as a slurry in water was charged to the autoclave. The autoclave lid was securely closed. The autoclave was evacuated and vacuum released with nitrogen.

This evacuation and releasing of vacuum was repeated three times. Then the same sequence of evacuation and releasing of vacuum with hydrogen was repeated two times. Finally, the autoclave was pressurized with hydrogen up to 7 kg/cm2 pressure. The temperature was maintained between ambient and 65° C. by application of steam/cooling water to the autoclave jacket as necessary. The pressure was maintained between 6.0 kg/cm2 and 7.0 kg/cm2 until a drop in pressure was no longer observed. The agitation was stopped, reaction mass allowed to settle and decanted from the catalyst by passage through a filter. The catalyst was washed with methanol by decantation and the washings were filtered. The combined filtrate and washings were charged into a 500-L SS kettle and methanol was distilled from it under reduced pressure up to 95-100° C. liquid temperature. The concentrate was cooled and extracted with toluene. The toluene extract was evaporated under vacuum.This gave 10 kg of L-norephedrine base. This was dissolved in 100 L of absolute ether and treated with ethanolic hydrogen chloride to give L-norephedrine HCl.m.p.

171-172° C., [α]D 25: -32.5° (5percent in water)Diastereomeric purity (HPLC): L-norephedrine: 97.5percent, L-norpseudoephedrine: 2.5percent With sodium hydroxide, hydrogen, Ni/Al/Fe catalyst in methanol, water, T= 20 - 65 °C , p= 4413.43 - 5149.01Torr , Product distribution / selectivity Patent; Emmellen Biotech Pharmaceuticals Limited; US2009/112025; (2009); (A1) English View in Reaxys

H

OH

H 2N HO

H

H

OH

H 2N H

H

N OH

Rx-ID: 28350948 View in Reaxys 4/63 Yield

Conditions & References 2 : Hydrogenation of L-Phenylacetylcarbinol-oxime with Commercial Raney Nickel Catalyst 11 kg of L-Phenylacetylcarbinol-oxime as a solution in 200 L of water-methanol mixture (30:70) was mixed with 6 kg of sodium hydroxide. The solution was charged to a high-pressure autoclave equipped with heating jacket and agitator. 5.5 kg of the commercial Raney nickel catalyst as slurry in water was charged to the autoclave. The autoclave lid was securely closed. The autoclave was evacuated and vacuum released with nitrogen. This evacuation and releasing of vacuum was repeated three times. Then the same sequence of evacuation and releasing of vacuum with hydrogen was repeated two times. Finally, the autoclave was pressurized with hydrogen upto 7 kg/cm2 pressure. The temperature was maintained between ambient and 65° C. by application of steam/cooling water to the autoclave jacket as necessary. The pressure was maintained between 6.0 kg/cm2 and 7.0 kg/cm2 until a drop in pressure was no longer observed. The agitation was stopped, reaction mass allowed to settle and decanted from the catalyst by passage through a filter. The catalyst was washed with methanol by decantation and the washings were filtered. The combined filtrate and washings were charged into a 500-L SS kettle and methanol was distilled from it under reduced pressure upto 95-100° C. liquid temperature. The concentrate was cooled and extracted with toluene. The toluene extract was evaporated under vacuum.This gave 10 kg of crude L-norephedrine base. This was dissolved in 100 L of absolute ether and treated with ethanolic hydrogen chloride. The reaction mass did not give crystalline Lnorephedrine HCl. HPLC analysis of the crude L-norephedrine base revealed that it contained L-norephedrine and Lnorpseudoephedrine bases in 55:45 ratio, in addition to several other peaks. Besides, a non-aqueous titration with 0.1 N perchloric acid showed only about 65percent of basic component of mol. wt. 151.20 (mol. wt of L-norephedrine/L-norpseudoephedrine).

With sodium hydroxide, hydrogen, nickel in methanol, water, T= 20 - 65 °C , p= 4413.43 - 5149.01Torr , Product distribution / selectivity

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

3/24

2016-04-27 15:52:06

Patent; Emmellen Biotech Pharmaceuticals Limited; US2009/112025; (2009); (A1) English View in Reaxys

O

OH

H

H N

NH 2 H

H 2N

H

HO

H

H

O

O

H HO

H 2N

Rx-ID: 10417330 View in Reaxys 5/63 Yield

Conditions & References Stage 1: With Hevea brasiliensis hydroxynitrile lyase in phosphate buffer, Time= 48h, T= 20 °C , pH= 7, Henry reaction Stage 2: With hydrogen, palladium on activated charcoal in ethanol, Time= 6h, T= 20 °C , Title compound not separated from byproducts Purkarthofer, Thomas; Gruber, Karl; Gruber-Khadjawi, Mandana; Waich, Kerstin; Skranc, Wolfgang; Mink, Daniel; Griengl, Herfried; Angewandte Chemie - International Edition; vol. 45; nb. 21; (2006); p. 3454 - 3456 View in Reaxys

O

OH

H

OH

H 2N

OH

H

NH 2

Rx-ID: 23597158 View in Reaxys 6/63 Yield

Conditions & References 2 :25 g of crude 1-erythro-2-amino-1-phenyl-1-propanol base is dissolved in 100 ml of a 1: 1 mixture of absolute ethanol and n-butanol. The mixture is heated to 60-65°. 20 g of benzoic acid is added to the mixture and the heating at 60-65° is continued for 2 hours. The mixture is cooled to 10° and the precipitate of l-erythro-2-amino-l-phenyl-lpropanol benzoate salt is filtered. This salt is suspended in 100 ml water and treated with 10 g of sodium hydroxide and the liberated pure l-erythro-2-amino-l-phenyl-l- propanol base is extracted with diethyl ether. Pure 1-erythro-2amino-1-phenyl-1- propanol base is recovered by evaporation of the solvent in vacuo. This yields 23 g of pure l-erythro-2-amino-l-phenyl-l-propanol base. This rnay be further converted to hydrochloride by treatment with ethanolic hydrochloride to give pure I-erythro-2-ainino-l'-phenyl-l-propanol hydrochloride,. mp: 173°, alphaD: -33.8° (5 percent in water). Diastereomeric purity (HPLC): 1-erythro-2-amino-1-phenyl-1-propanol: 99.8 percent, 1- thero-2-amino-1phenyl-1-propanol: 0.2 percent With sodium hydroxide in water Patent; EMMELLEN BIOTECH PHARMACEUTICALS LIMITED; WO2005/100299; (2005); (A1) English View in Reaxys

H

OH

H N

OH

H 2N H

H H

Rx-ID: 25391315 View in Reaxys 7/63 Yield

Conditions & References 2 : Example 2 Example 2 L-erythro-(1R,2S)-2-amino-1-phenylpropan-1-ol A mixture of L-erythro-(1R,2S)-2-(N-benzylamino)-1-phenylpropan-1-ol (3.00 g) obtained in Example 1, 20percent Pd(OH)2/C (0.62 g) and methanol (124 ml) was stirred for 7.3 hours at 24°C under hydrogen atmosphere (5 kg/cm2).

The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to obtain L-erythro-(1R, 2S)-2-amino-1-phenylpropan-1-ol (1.83 g).

1H-NMR (400 MHz) δ(CDCl ): 0.94 (3H, d, J=6.8 Hz), 1.90-2.60 (3H, m), 3.08 (1H, dd, J=4.8 Hz, 6.8 Hz), 4.44 (1H, 3 d, J=4.8 Hz), 7.20-7.40 (10H, m) ppm.

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

4/24

2016-04-27 15:52:06

With Pd(OH)2/C in methanol Patent; NAGASE and COMPANY, LTD.; EP1142864; (2001); (A1) English View in Reaxys

H

OH

H 2N HO

H

H 2N

H

O

Rx-ID: 25391314 View in Reaxys 8/63 Yield

Conditions & References 3 : Example 3 Example 3 L-erythro-(1R,2S)-2-amino-1-phenylpropan-1-ol A mixture of L-(R) -phenylacetylcarbinol (purity 79.1percent; 4.75 g, 25.0 mmol), benzylamine (2.68 g, 25 mmol), 20percent Pd(OH)2(1.00 g) and methanol (47 ml) was stirred for 6 hours at 50°C under hydrogen atmosphere (5 kg/cm2).

The reaction mixture was filtered and the residue was washed with methanol.

The filtrate and the washed liquor were combined and concentrated under reduced pressure to obtain crude L-erythro-(1R,2S)-2-amino-1-phenylpropan-1-ol (5.67 g).

Erythro:threo = 88.3:11.7.

With Pd(OH)2 in methanol Patent; NAGASE and COMPANY, LTD.; EP1142864; (2001); (A1) English View in Reaxys

O O

O S

H

H

NH H

OH

H 2N H

Rx-ID: 33637646 View in Reaxys 9/63 Yield

Conditions & References

71.5 %

With lithium aluminium tetrahydride in tetrahydrofuran, Time= 1h, T= 0 - 20 °C , optical yield given as percent ee Lee, Hyeon-Kyu; Kang, Soyeong; Choi, Eun Bok; Journal of Organic Chemistry; vol. 77; nb. 12; (2012); p. 5454 5460 View in Reaxys

HO

H N

O

OH

H Cl

H

H 2N H

Rx-ID: 20280774 View in Reaxys 10/63 Yield

Conditions & References Reaction Steps: 2 1: NaBH4 / methanol 2: Zn, 1 N aq. HCl, AcOH With hydrogenchloride, sodium tetrahydroborate, acetic acid, zinc in methanol Oppolzer, Wolfgang; Tamura, Osamu; Sundarababu, Gajendran; Signer, Marcel; Journal of the American Chemical Society; vol. 114; nb. 14; (1992); p. 5900 - 5902 View in Reaxys

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

5/24

2016-04-27 15:52:06

Z O S N

H

N

O

OH

H 2N

O

H

O

Rx-ID: 20284996 View in Reaxys 11/63 Yield

Conditions & References Reaction Steps: 3 1: 1 N aq. HCl 2: NaBH4 / methanol 3: Zn, 1 N aq. HCl, AcOH With hydrogenchloride, sodium tetrahydroborate, acetic acid, zinc in methanol Oppolzer, Wolfgang; Tamura, Osamu; Sundarababu, Gajendran; Signer, Marcel; Journal of the American Chemical Society; vol. 114; nb. 14; (1992); p. 5900 - 5902 View in Reaxys

H

O

platinum

OH

H 2N H

Rx-ID: 20290995 View in Reaxys 12/63 Yield

Conditions & References Reaction Steps: 4 1: 1.) LiN(TMS)2, 2.) ZnCl2 2: 1 N aq. HCl 3: NaBH4 / methanol 4: Zn, 1 N aq. HCl, AcOH With hydrogenchloride, sodium tetrahydroborate, acetic acid, zinc(II) chloride, lithium hexamethyldisilazane, zinc in methanol Oppolzer, Wolfgang; Tamura, Osamu; Sundarababu, Gajendran; Signer, Marcel; Journal of the American Chemical Society; vol. 114; nb. 14; (1992); p. 5900 - 5902 View in Reaxys

H N

O

OH

OH

H

H HO

H 2N

NH 2 H

H

O

Rx-ID: 3043727 View in Reaxys 13/63 Yield

Conditions & References With potassium hydroxide in methanol, water, Time= 2h, Heating, Yields of byproduct given Buckley, Thomas F.; Rapoport, Henry; Journal of the American Chemical Society; vol. 103; nb. 20; (1981); p.

6157 - 6163 View in Reaxys

H N

O O

OH

H

OH

H 2N H

Rx-ID: 3985502 View in Reaxys 14/63

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

6/24

2016-04-27 15:52:06

Yield

Conditions & References

72 %

With trifluoroacetic acid in dichloromethane, Time= 3h, Ambient temperature Jommi, Giancarlo; Ripa, Alberto; Ripa, Giorgio; Sisti, Massimo; Gazzetta Chimica Italiana; vol. 118; nb. 1; (1988); p. 75 - 76 View in Reaxys

H

Si

OH

H 2N

O

H

H 2N

Rx-ID: 2265867 View in Reaxys 15/63 Yield

Conditions & References With hydrogen fluoride in acetonitrile, Time= 17h, T= 50 °C , or LiAlH4, 1h, reflux Brussee; Dofferhoff; Kruse; Van der Gen; Tetrahedron; vol. 46; nb. 5; (1990); p. 1653 - 1658 View in Reaxys

OH

H

E N

OH

H 2N

H

OH

H 2N H

H

OH

Rx-ID: 23597159 View in Reaxys 16/63 Yield

Conditions & References 1.1B; 4 :25 g of sodium hydroxide is dissolved in 350 ml of water. 50 g of 1-1-phenyl-1- hydroxy-2-propanone oxime is added to it. The solution is chilled to -15°C. 30 g of the nickel aluminium catalyst mixture (containing 60 parts by weight of aluminium and 40 parts by weight of nickel) is added to it. The mixture is vigorously stirred at -15°C and then the temperature is allowed to rise as a free exotherm sets in. When the temperature reaches 75°, the exothermic tendency of reaction mixture subsides. 200 ml of 1,2-dichloroethane is added to the mixture and the catalyst sludge is filtered. 1,2- Dichloroethane is separated from the filtrate and aqueous layer is extracted again with 100 ml of 1,2-dichloroethane. The combined organic layer is washed with 100 ml water, dried over sodium sulphate and solvent removed in vacuo. This gives 50 g of l-erythro-2-amino-l-phenyl-l-propanol base. This is dissolved in absolute ether and treated with ethanolic hydrogen chloride to give I-erythro-2-amino- 1-phenyl-1-propanol hydrochloric acid. mp 171-172°, alphaD : -32.5° (5 percent in water) Diastereomeric purity (HPLC): 1-erythro-2-amino-1-phenyl-1-propanol: 97.5 percent, 1- thero-2-amino-1-phenyl-1-propanol: 2.5 percent; 25 g of sodium hydroxide is dissolved in 350 ml of water. 50 g of 1-1-phenyl-1- hydroxy-2-propanone oxime is added to it. The solution is chilled to -15°C. 20 g of the nickel aluminium catalyst mixture (containing 60 parts by weight of aluminium and 40 parts by weight of nickel) is added to it. The mixture is vigorously stirred at -15°C and then the temperature is allowed to rise. An exotherm sets in and temperature increases upto 55°C. 200 ml of 1,2-dichloroethane is added to the mixture and the catalyst sludge is filtered. 1,2-Dichloroethane is separated from the filtrate and aqueous layer is extracted again with 100 ml of 1,2-dichloroethane. The combined organic layer is washed with 100 ml water, dried over sodium sulphate and solvent removed in vacuo. This gives 38 g of l-erythro-2-amino-l-phenyl-l-propanol base. This is dissolved in absolute ether and treated with ethanolic hydrogen chloride to give I-erythro-2-amino- 1-phenyl-1-propanol hydrochloric acid. mp 171-172°, alphaD : -31.5° (5 percent in water) Diastereomeric purity (HPLC): 1-erythro- 2-amino-1-phenyl-1propanol: 96.8 (at)percent,1-thero-2-amino-1-phenyl-1-propanol: 3.2 percent With sodium hydroxide, Al(b),Ni(60) (W), water, T= -15 - 75 °C , Product distribution / selectivity Patent; EMMELLEN BIOTECH PHARMACEUTICALS LIMITED; WO2005/100299; (2005); (A1) English View in Reaxys 3.3B :25 g of sodium hydroxide is dissolved in 350 ml of water. 50 g of 1-1-phenyl-1- hydroxy-2-propanone oxime is added to it. The solution is chilled to -15°C. 30 g of the nickel aluminium catalyst mixture (containing 85 parts by weight of aluminium and 15 parts by weight of nickel) is added to it. The mixture is vigorously stirred at -15°C and then the temperature is allowed to rise. An exotherm sets in and temperature increases upto 95°C. 200 ml of 1,2dichloroethane is added to the mixture and the catalyst sludge is filtered. 1,2-Dichloroethane is separated from the filtrate and aqueous layer is extracted again with 100 ml of 1,2-dichloroethane. The combined organic layer is washed with 100 ml water, dried over sodium sulphate and solvent removed in vacuo. This gives 22.5 g of l-erythro-2amino-l-phenyl-l-propanol base. This is dissolved in absolute ether and treated with ethanolic hydrogen chloride to

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

7/24

2016-04-27 15:52:06

give 1-erythro-2-amino- 1-phenyl-1-propanol hydrochloric acid. mp 167-169°, alphaD : -27.0° (5 percent in water) Diastereomeric purity (HPLC) : 1-erythro- 2-amino-l-phenyl-l-propanol: 86.5 percent, 1-thero-2-amino-1-phenyl-1-propanol: 13.5 percent With sodium hydroxide, Al(b),Ni(15) (W), water, T= -15 - 95 °C , Product distribution / selectivity Patent; EMMELLEN BIOTECH PHARMACEUTICALS LIMITED; WO2005/100299; (2005); (A1) English View in Reaxys 3.3A :25 g of sodium hydroxide is dissolved in 350 ml of water. 50 g of 1-1-phenyl-1- hydroxy-2-propanone oxime is added to it. The solution is chilled to -15°C. 30 g of the nickel aluminium catalyst mixture (containing 55 parts by weight of aluminium and 45 parts by weight of nickel) is added to it. The mixture is vigorously stirred at-15°C and then the temperature is allowed to rise. An exotherm sets in and temperature in creases upto 35°C. 200 ml of 1,2dichloroethane is added to the mixture and the catalyst sludge is filtered. 1,2-Dichloroethane is separated from the filtrate and aqueous layer is extracted again with 100 ml of 1,2-dichloroethane. The combined organic layer is washed with 100 ml water, dried over sodium sulphate and solvent removed in vacuo. This gives 29 g of l-erythro-2-amino- I -phenyl- I -propanol base. This is dissolved in absolute ether and treated with ethanolic hydrogen chloride to give I-eqthro-2-anlino- I -phenyl- I -propanol hydrochloric acid. mp 163-165°, alphaD : -26.5° (5 percent in water) Diastereomeric purity (HPLC): 1-erythro-2-amino-1-phenyl-1-propanol: 83.8 percent, 1- thero-2-amino-1-phenyl-1-propanol: 16.2 percent With sodium hydroxide, Al(b),Ni(45) (W), water, T= -15 - 35 °C , Product distribution / selectivity Patent; EMMELLEN BIOTECH PHARMACEUTICALS LIMITED; WO2005/100299; (2005); (A1) English View in Reaxys

OH

H N

HO

OH

H H 2N

H

Rx-ID: 3089267 View in Reaxys 17/63 Yield

Conditions & References With hydrogenchloride, acetic acid, zinc, Yield given Oppolzer, Wolfgang; Tamura, Osamu; Sundarababu, Gajendran; Signer, Marcel; Journal of the American Chemical Society; vol. 114; nb. 14; (1992); p. 5900 - 5902 View in Reaxys

OH

H

HO

H HO

H 2N

NH 2 H

H

HN N

Rx-ID: 3611773 View in Reaxys 18/63 Yield

Conditions & References With hydrogenchloride in water, Time= 48h, T= 100 °C , Yield given. Yields of byproduct given Lamant; Guignard; Helvetica Chimica Acta; vol. 70; nb. 5; (1987); p. 1279 - 1285 View in Reaxys

O H 2N

H

OH

H 2N

H

H

Rx-ID: 38002600 View in Reaxys 19/63 Yield

Conditions & References With alcohol dehydrogenase from Ralstonia sp. in aq. buffer, T= 21 °C , Enzymatic reaction

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

8/24

2016-04-27 15:52:06

Sehl, Torsten; Hailes, Helen C.; Ward, John M.; Menyes, Ulf; Pohl, Martina; Rother, Doerte; Green Chemistry; vol. 16; nb. 6; (2014); p. 3341 - 3348 View in Reaxys

O

OH

H H 2N

H 2N

H

OH

H 2N H

H

Rx-ID: 38002607 View in Reaxys 20/63 Yield

Conditions & References With alcohol dehydrogenase from Ralstonia sp. in aq. buffer, T= 21 °C , Enzymatic reaction Sehl, Torsten; Hailes, Helen C.; Ward, John M.; Menyes, Ulf; Pohl, Martina; Rother, Doerte; Green Chemistry; vol. 16; nb. 6; (2014); p. 3341 - 3348 View in Reaxys With alcohol dehydrogenase from Ralstonia sp. in aq. buffer, T= 21 °C , Enzymatic reaction Sehl, Torsten; Hailes, Helen C.; Ward, John M.; Menyes, Ulf; Pohl, Martina; Rother, Doerte; Green Chemistry; vol. 16; nb. 6; (2014); p. 3341 - 3348 View in Reaxys

O

OH

H H 2N

O

H

Rx-ID: 17238837 View in Reaxys 21/63 Yield

Conditions & References Reaction Steps: 3 2: baker's yeast/montmorillonite K10, 2percent aq. KCl, sucrose / 24 h / 30 °C 3: NaBH4/FeCl3 / tetrahydrofuran / 24 h / Ambient temperature With sodium tetrahydroborate, baker's yeast, Montmorillonite K10, potassium chloride, iron(III) chloride, [14C]-Sucrose in tetrahydrofuran Kreutz, Olyr C.; Moran, Paulo J. S.; Rodrigues, J. Augusto R.; Tetrahedron Asymmetry; vol. 8; nb. 15; (1997); p.

2649 - 2653 View in Reaxys Reaction Steps: 2 1: S-(-)-N-methyl-alpha-methylbenzylamine; Cv-(S)-ω-transaminase / aq. buffer / 21 °C / |Enzymatic reaction 2: alcohol dehydrogenase from Ralstonia sp. / aq. buffer / 21 °C / |Enzymatic reaction With S-(-)-N-methyl-alpha-methylbenzylamine, alcohol dehydrogenase from Ralstonia sp., Cv-(S)-ω-transaminase in aq. buffer Sehl, Torsten; Hailes, Helen C.; Ward, John M.; Menyes, Ulf; Pohl, Martina; Rother, Doerte; Green Chemistry; vol. 16; nb. 6; (2014); p. 3341 - 3348 View in Reaxys

OH H

H

OH

H 2N H

N

Rx-ID: 17291088 View in Reaxys 22/63 Yield

Conditions & References Reaction Steps: 2 1: pyridine / diethyl ether 2: 2.) NaBH4, 3.) H2O, H+ / 1.) Et2O With pyridine, sodium tetrahydroborate, water, hydrogen cation in diethyl ether

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

9/24

2016-04-27 15:52:06

Effenberger, Franz; Gutterer, Beate; Jaeger, Juergen; Tetrahedron Asymmetry; vol. 8; nb. 3; (1997); p. 459 - 467 View in Reaxys Reaction Steps: 2 1: 70 percent / pyridine / 4 h / Ambient temperature 2: 2) NaBH4 / 1) Et2O, 12 h, room temperature, 2) THF, MeOH, -50 deg C, 4 h With pyridine, sodium tetrahydroborate Effenberger, Franz; Gutterer, Beate; Ziegler, Thomas; Liebigs Annalen der Chemie; nb. 3; (1991); p. 269 - 273 View in Reaxys

H

OH

H 2N HO

H HO

NH 2 H

H

H

O

Rx-ID: 35891579 View in Reaxys 23/63 Yield

Conditions & References With (S)-1-phenyl-ethylamine, pyridoxal 5'-phosphate, Chromobacterium violaceum ω-transaminase in aq. buffer, Time= 16h, T= 20 °C , pH= 7.5, Enzymatic reaction, Overall yield = 85 percent; Overall yield = 121 mg Sehl, Torsten; Hailes, Helen C.; Ward, John M.; Wardenga, Rainer; Von Lieres, Eric; Offermann, Heike; Westphal, Robert; Pohl, Martina; Rother, Doerte; Angewandte Chemie - International Edition; vol. 52; nb. 26; (2013); p.

6772 - 6775; Angew. Chem.; vol. 125; nb. 26; (2013); p. 6904 - 6908,5 View in Reaxys

H

OH

H 2N HO

H

H

O

Rx-ID: 437482 View in Reaxys 24/63 Yield

Conditions & References With ethanol, ammonia, palladium, Hydrogenation Patent; I.G. Farbenind.; DE587586; (1930); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 20; p. 963 View in Reaxys With methanol, ammonium chloride, nickel, Hydrogenation Patent; I.G. Farbenind.; DE599433; (1930); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 20; p. 691 View in Reaxys Reaction Steps: 2 2: acetic acid; palladium / Hydrogenation With palladium, acetic acid Patent; I.G. Farbenind.; DE587586; (1930); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 20; p. 963 View in Reaxys With [3H]-L-Alanine, pyridoxal 5'-phosphate, Chromobacterium violaceum ω-transaminase, Thiamine pyrophosphate, Adenine-flavine dinucleotide, magnesium chloride in aq. buffer, Time= 24h, T= 20 °C , pH= 7.5, Enzymatic reaction, Equilibrium constant, Concentration Sehl, Torsten; Hailes, Helen C.; Ward, John M.; Wardenga, Rainer; Von Lieres, Eric; Offermann, Heike; Westphal, Robert; Pohl, Martina; Rother, Doerte; Angewandte Chemie - International Edition; vol. 52; nb. 26; (2013); p.

6772 - 6775; Angew. Chem.; vol. 125; nb. 26; (2013); p. 6904 - 6908,5 View in Reaxys With S-(-)-N-methyl-alpha-methylbenzylamine, Cv-(S)-ω-transaminase in aq. buffer, T= 25 °C , Enzymatic reaction

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

10/24

2016-04-27 15:52:06

Sehl, Torsten; Hailes, Helen C.; Ward, John M.; Menyes, Ulf; Pohl, Martina; Rother, Doerte; Green Chemistry; vol. 16; nb. 6; (2014); p. 3341 - 3348 View in Reaxys

OH O

H

NE

OH

H 2N

H

OH

H 2N H

H

Rx-ID: 4742198 View in Reaxys 25/63 Yield

Conditions & References With lithium aluminium tetrahydride in tetrahydrofuran, Time= 24h, Heating, Yield given. Yields of byproduct given.

Title compound not separated from byproducts Kreutz, Olyr C.; Moran, Paulo J. S.; Rodrigues, J. Augusto R.; Tetrahedron Asymmetry; vol. 8; nb. 15; (1997); p.

2649 - 2653 View in Reaxys With sodium tetrahydroborate, iron(III) chloride in tetrahydrofuran, Time= 24h, Ambient temperature, Yield given.

Yields of byproduct given. Title compound not separated from byproducts Kreutz, Olyr C.; Moran, Paulo J. S.; Rodrigues, J. Augusto R.; Tetrahedron Asymmetry; vol. 8; nb. 15; (1997); p.

2649 - 2653 View in Reaxys

O HO

H

NE

OH

H 2N H

Rx-ID: 17199958 View in Reaxys 26/63 Yield

Conditions & References Reaction Steps: 3 1: 96 percent / Ag2O / CH2Cl2 / 0.5 h / 0 °C 2: baker's yeast/montmorillonite K10, 2percent aq. KCl, sucrose / 24 h / 30 °C 3: NaBH4/FeCl3 / tetrahydrofuran / 24 h / Ambient temperature With sodium tetrahydroborate, baker's yeast, Montmorillonite K10, potassium chloride, iron(III) chloride, silver(l) oxide, [14C]-Sucrose in tetrahydrofuran, dichloromethane Kreutz, Olyr C.; Moran, Paulo J. S.; Rodrigues, J. Augusto R.; Tetrahedron Asymmetry; vol. 8; nb. 15; (1997); p.

2649 - 2653 View in Reaxys

O O

H

NE

OH

H 2N H

Rx-ID: 17233208 View in Reaxys 27/63 Yield

Conditions & References Reaction Steps: 2 1: baker's yeast/montmorillonite K10, 2percent aq. KCl, sucrose / 24 h / 30 °C 2: NaBH4/FeCl3 / tetrahydrofuran / 24 h / Ambient temperature With sodium tetrahydroborate, baker's yeast, Montmorillonite K10, potassium chloride, iron(III) chloride, [14C]-Sucrose in tetrahydrofuran Kreutz, Olyr C.; Moran, Paulo J. S.; Rodrigues, J. Augusto R.; Tetrahedron Asymmetry; vol. 8; nb. 15; (1997); p.

2649 - 2653 View in Reaxys

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

11/24

2016-04-27 15:52:06

N

H Si

OH

H 2N

O

H

Rx-ID: 21920964 View in Reaxys 28/63 Yield

Conditions & References Reaction Steps: 2 1: 2) NaBH4 / 1) ether, 4 h, reflux, 2) methanol, rt 2: 40percent aq. HF / acetonitrile / 17 h / 50 °C / or LiAlH4, 1h, reflux With sodium tetrahydroborate, hydrogen fluoride in acetonitrile Brussee; Dofferhoff; Kruse; Van der Gen; Tetrahedron; vol. 46; nb. 5; (1990); p. 1653 - 1658 View in Reaxys

O

H

H 2N

H

OH

HO

H 2N

NH 2 H

H

H

Rx-ID: 29581125 View in Reaxys 29/63 Yield

Conditions & References With 1,3-bis[tris(hydroxymethyl)methylamino]-propane, Ephedra sinica Stapf (S)-cathinone reductase, glycerol, Reduced nicotinamide-adenine dinucleotide, threo-1,4-dimercapto-2,3-butanediol, Time= 1h, T= 37 °C , pH= 8.5, aq. buffer, Enzymatic reaction Krizevski, Raz; Bar, Einat; Shalit, Or; Sitrit, Yaron; Ben-Shabat, Shimon; Lewinsohn, Efraim; Phytochemistry; vol. 71; nb. 8-9; (2010); p. 895 - 903 View in Reaxys

H

O

OH

H 2N H

HN N

Rx-ID: 18886265 View in Reaxys 30/63 Yield

Conditions & References Reaction Steps: 2 1: 94 percent / NaBH4 / methanol / 24 h / -78 °C 2: 2.5N HCl / H2O / 48 h / 100 °C With hydrogenchloride, sodium tetrahydroborate in methanol, water Lamant; Guignard; Helvetica Chimica Acta; vol. 70; nb. 5; (1987); p. 1279 - 1285 View in Reaxys

H

H

OH

H 2N

O

H

Rx-ID: 38002582 View in Reaxys 31/63 Yield

Conditions & References Reaction Steps: 2 1: AHAS-I from E.coli / aq. buffer / 1.5 h / 25 °C / |Enzymatic reaction 2: S-(-)-N-methyl-alpha-methylbenzylamine; Cv-(S)-ω-transaminase / aq. buffer / 25 °C / |Enzymatic reaction

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

12/24

2016-04-27 15:52:06

With S-(-)-N-methyl-alpha-methylbenzylamine, AHAS-I from E.coli, Cv-(S)-ω-transaminase in aq. buffer Sehl, Torsten; Hailes, Helen C.; Ward, John M.; Menyes, Ulf; Pohl, Martina; Rother, Doerte; Green Chemistry; vol. 16; nb. 6; (2014); p. 3341 - 3348 View in Reaxys Reaction Steps: 2 1: (S)-selective carboligase ApPDC variant E469G / aq. phosphate buffer / 48 h / 25 °C / pH 7 / |Enzymatic reaction 2: S-(-)-N-methyl-alpha-methylbenzylamine; Cv-(S)-ω-transaminase / aq. buffer / 25 °C / |Enzymatic reaction With S-(-)-N-methyl-alpha-methylbenzylamine, (S)-selective carboligase ApPDC variant E469G, Cv-(S)-ω-transaminase in aq. phosphate buffer Sehl, Torsten; Hailes, Helen C.; Ward, John M.; Menyes, Ulf; Pohl, Martina; Rother, Doerte; Green Chemistry; vol. 16; nb. 6; (2014); p. 3341 - 3348 View in Reaxys

OH

H HO

H 2N H

N

Rx-ID: 2659630 View in Reaxys 32/63 Yield

Conditions & References With potassium hydroxide, hydroxylamine hydrochloride in methanol, water, Time= 48h, Heating, Yield given Kashima, Choji; Maruyama, Tatsuya; Fujioka, Yoko; Harada, Kazuo; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1989); p. 1041 - 1046 View in Reaxys

OH

H

O O

H 2N N

H

O O

Rx-ID: 18163968 View in Reaxys 33/63 Yield

Conditions & References Reaction Steps: 2 1: 71 percent / 0.25N NaOH / methanol / 1.5 h / 0 °C 2: 72 percent / TFA / CH2Cl2 / 3 h / Ambient temperature With sodium hydroxide, trifluoroacetic acid in methanol, dichloromethane Jommi, Giancarlo; Ripa, Alberto; Ripa, Giorgio; Sisti, Massimo; Gazzetta Chimica Italiana; vol. 118; nb. 1; (1988); p. 75 - 76 View in Reaxys O HO

N

S O

Cl H

OH

H 2N H

Rx-ID: 33637622 View in Reaxys 34/63 Yield

Conditions & References Reaction Steps: 3 1: toluene-4-sulfonic acid / toluene / 0.5 h / Reflux 2: formic acid; (R,R)-RhCl(TsDPEN)Cp*; triethylamine / ethyl acetate / 0.25 h / 20 °C 3: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 - 20 °C

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

13/24

2016-04-27 15:52:06

With lithium aluminium tetrahydride, formic acid, (R,R)-RhCl(TsDPEN)Cp*, toluene-4-sulfonic acid, triethylamine in tetrahydrofuran, ethyl acetate, toluene Lee, Hyeon-Kyu; Kang, Soyeong; Choi, Eun Bok; Journal of Organic Chemistry; vol. 77; nb. 12; (2012); p. 5454 5460 View in Reaxys O

O S

O

N

OH

H H 2N

H

Rx-ID: 33637638 View in Reaxys 35/63 Yield

Conditions & References Reaction Steps: 2 1: formic acid; (R,R)-RhCl(TsDPEN)Cp*; triethylamine / ethyl acetate / 0.25 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 - 20 °C With lithium aluminium tetrahydride, formic acid, (R,R)-RhCl(TsDPEN)Cp*, triethylamine in tetrahydrofuran, ethyl acetate Lee, Hyeon-Kyu; Kang, Soyeong; Choi, Eun Bok; Journal of Organic Chemistry; vol. 77; nb. 12; (2012); p. 5454 5460 View in Reaxys

N H

OH

H 2N H

Si O

Rx-ID: 33637669 View in Reaxys 36/63 Yield

Conditions & References Reaction Steps: 5 1: diethyl ether / 4 h / Reflux 2: amidosulfonyl chloride / N,N-dimethyl acetamide / 1 h / 20 °C 3: toluene-4-sulfonic acid / toluene / 0.5 h / Reflux 4: formic acid; (R,R)-RhCl(TsDPEN)Cp*; triethylamine / ethyl acetate / 0.25 h / 20 °C 5: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 - 20 °C With lithium aluminium tetrahydride, formic acid, diethyl ether, (R,R)-RhCl(TsDPEN)Cp*, amidosulfonyl chloride, toluene-4-sulfonic acid, triethylamine in tetrahydrofuran, N,N-dimethyl acetamide, ethyl acetate, toluene Lee, Hyeon-Kyu; Kang, Soyeong; Choi, Eun Bok; Journal of Organic Chemistry; vol. 77; nb. 12; (2012); p. 5454 5460 View in Reaxys

H

OH

H 2N HO

H

H

O

Rx-ID: 33637683 View in Reaxys 37/63 Yield

Conditions & References Reaction Steps: 4 1: amidosulfonyl chloride / N,N-dimethyl acetamide / 1 h / 20 °C 2: toluene-4-sulfonic acid / toluene / 0.5 h / Reflux 3: formic acid; (R,R)-RhCl(TsDPEN)Cp*; triethylamine / ethyl acetate / 0.25 h / 20 °C 4: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 - 20 °C With lithium aluminium tetrahydride, formic acid, (R,R)-RhCl(TsDPEN)Cp*, amidosulfonyl chloride, toluene-4-sulfonic acid, triethylamine in tetrahydrofuran, N,N-dimethyl acetamide, ethyl acetate, toluene

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

14/24

2016-04-27 15:52:06

Lee, Hyeon-Kyu; Kang, Soyeong; Choi, Eun Bok; Journal of Organic Chemistry; vol. 77; nb. 12; (2012); p. 5454 5460 View in Reaxys

OH

H

O

H 2N H

HO Br racemate

Rx-ID: 41227705 View in Reaxys 38/63 Yield

Conditions & References Reaction Steps: 6 1.1: sodium hydroxide / tetrahydrofuran / 2 h / 0 °C 2.1: (S,S)-(salen)Co(OAc) complex / water; tetrahydrofuran / 14 h / 0 - 25 °C 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 25 °C 4.1: triethylamine / dichloromethane / 0.08 h / 0 °C 4.2: 0.08 h / 0 °C 5.1: sodium azide / DMFA / 12 h / 80 °C 6.1: palladium 10 on activated carbon; hydrogen / methanol / 12 h / 20 °C / 760.05 Torr With lithium aluminium tetrahydride, sodium azide, (S,S)-(salen)Co(OAc) complex, palladium 10 on activated carbon, hydrogen, triethylamine, sodium hydroxide in tetrahydrofuran, methanol, dichloromethane, water, DMFA Lalwani, Komal G.; Sudalai, Arumugam; Tetrahedron Letters; vol. 56; nb. 46; (2015); p. 6488 - 6490 View in Reaxys

OH

H

O

H 2N H

O

racemate

Rx-ID: 41227717 View in Reaxys 39/63 Yield

Conditions & References Reaction Steps: 5 1.1: (S,S)-(salen)Co(OAc) complex / water; tetrahydrofuran / 14 h / 0 - 25 °C 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 25 °C 3.1: triethylamine / dichloromethane / 0.08 h / 0 °C 3.2: 0.08 h / 0 °C 4.1: sodium azide / DMFA / 12 h / 80 °C 5.1: palladium 10 on activated carbon; hydrogen / methanol / 12 h / 20 °C / 760.05 Torr With lithium aluminium tetrahydride, sodium azide, (S,S)-(salen)Co(OAc) complex, palladium 10 on activated carbon, hydrogen, triethylamine in tetrahydrofuran, methanol, dichloromethane, water, DMFA Lalwani, Komal G.; Sudalai, Arumugam; Tetrahedron Letters; vol. 56; nb. 46; (2015); p. 6488 - 6490 View in Reaxys

H

OH

H 2N

O

H O

Rx-ID: 41227726 View in Reaxys 40/63 Yield

Conditions & References Reaction Steps: 4

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

15/24

2016-04-27 15:52:06

1.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 25 °C 2.1: triethylamine / dichloromethane / 0.08 h / 0 °C 2.2: 0.08 h / 0 °C 3.1: sodium azide / DMFA / 12 h / 80 °C 4.1: palladium 10 on activated carbon; hydrogen / methanol / 12 h / 20 °C / 760.05 Torr With lithium aluminium tetrahydride, sodium azide, palladium 10 on activated carbon, hydrogen, triethylamine in tetrahydrofuran, methanol, dichloromethane, DMFA Lalwani, Komal G.; Sudalai, Arumugam; Tetrahedron Letters; vol. 56; nb. 46; (2015); p. 6488 - 6490 View in Reaxys

OH

H H 2N

O

H

OH

Rx-ID: 41227735 View in Reaxys 41/63 Yield

Conditions & References Reaction Steps: 3 1.1: triethylamine / dichloromethane / 0.08 h / 0 °C 1.2: 0.08 h / 0 °C 2.1: sodium azide / DMFA / 12 h / 80 °C 3.1: palladium 10 on activated carbon; hydrogen / methanol / 12 h / 20 °C / 760.05 Torr With sodium azide, palladium 10 on activated carbon, hydrogen, triethylamine in methanol, dichloromethane, DMFA Lalwani, Komal G.; Sudalai, Arumugam; Tetrahedron Letters; vol. 56; nb. 46; (2015); p. 6488 - 6490 View in Reaxys

H

HO

OH

H 2N H

Rx-ID: 41227763 View in Reaxys 42/63 Yield

Conditions & References Reaction Steps: 7 1.1: N-Bromosuccinimide / acetonitrile / 25 °C 2.1: sodium hydroxide / tetrahydrofuran / 2 h / 0 °C 3.1: (S,S)-(salen)Co(OAc) complex / water; tetrahydrofuran / 14 h / 0 - 25 °C 4.1: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 25 °C 5.1: triethylamine / dichloromethane / 0.08 h / 0 °C 5.2: 0.08 h / 0 °C 6.1: sodium azide / DMFA / 12 h / 80 °C 7.1: palladium 10 on activated carbon; hydrogen / methanol / 12 h / 20 °C / 760.05 Torr With N-Bromosuccinimide, lithium aluminium tetrahydride, sodium azide, (S,S)-(salen)Co(OAc) complex, palladium 10 on activated carbon, hydrogen, triethylamine, sodium hydroxide in tetrahydrofuran, methanol, dichloromethane, water, DMFA, acetonitrile Lalwani, Komal G.; Sudalai, Arumugam; Tetrahedron Letters; vol. 56; nb. 46; (2015); p. 6488 - 6490 View in Reaxys

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

16/24

2016-04-27 15:52:06

OH

H H 2N

O

H O

O

S

O

Rx-ID: 41227781 View in Reaxys 43/63 Yield

Conditions & References Reaction Steps: 2 1: sodium azide / DMFA / 12 h / 80 °C 2: palladium 10 on activated carbon; hydrogen / methanol / 12 h / 20 °C / 760.05 Torr With sodium azide, palladium 10 on activated carbon, hydrogen in methanol, DMFA Lalwani, Komal G.; Sudalai, Arumugam; Tetrahedron Letters; vol. 56; nb. 46; (2015); p. 6488 - 6490 View in Reaxys

H 2N

H

HO

H

H

OH

H 2N H

racemate

Rx-ID: 437465 View in Reaxys 44/63 Yield

Conditions & References With phenyl-hydroxy-acetic acid Jarowski; Hartung; Journal of Organic Chemistry; vol. 8; (1943); p. 564,566 View in Reaxys

H HO

H

OH

HO

H 2N

NH 2 H

H N

Rx-ID: 2659628 View in Reaxys 45/63 Yield

Conditions & References With potassium hydroxide, hydroxylamine hydrochloride in methanol, water, Time= 48h, Heating, Yield given. Yields of byproduct given Kashima, Choji; Maruyama, Tatsuya; Fujioka, Yoko; Harada, Kazuo; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1989); p. 1041 - 1046 View in Reaxys

O

H

EN O

OH

H 2N

H

OH

H

H HO

H 2N

NH 2 H

H 2N

H

HO

H

H

Rx-ID: 5029024 View in Reaxys 46/63 Yield

Conditions & References With dimethylsulfide borane complex, chiral amino alcohol derived from (-)-α-pinene B(OMe)3 in tetrahydrofuran, 0-5 deg C, 2 h, reflux, 18 h, Title compound not separated from byproducts Masui, Moriyasu; Shioiri, Takayuki; Tetrahedron Letters; vol. 39; nb. 29; (1998); p. 5195 - 5198

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

17/24

2016-04-27 15:52:06

View in Reaxys

N

OH

H

1.) CH3MgX

H 2N H

Si O

Rx-ID: 7363072 View in Reaxys 47/63 Yield

Conditions & References With sodium tetrahydroborate, water, hydrogen cation, 1.) Et2O, Multistep reaction Effenberger, Franz; Gutterer, Beate; Jaeger, Juergen; Tetrahedron Asymmetry; vol. 8; nb. 3; (1997); p. 459 - 467 View in Reaxys

OH

H

(S)-2-amino-1-phenyl-propan-1-on<(1S)-2-oxo-bornane-10-sulfonate>

H 2N H

Rx-ID: 7363073 View in Reaxys 48/63 Yield

Conditions & References With palladium on activated charcoal, water, Hydrogenation Takamatsu; Yakugaku Zasshi; vol. 76; (1956); p. 1227; ; (1957); p. 4304 View in Reaxys

H

(S)-2-amino-1-phenyl-propanone-(1)-L-mandelate

OH

H 2N H

Rx-ID: 7363074 View in Reaxys 49/63 Yield

Conditions & References With water, palladium, Hydrogenation Patent; I.G. Farbenind.; DE639126; (1935); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 23; p. 481 View in Reaxys

HO

H

erythro H 2N

Cl

H

erythro

OH

HO

H 2N H

Cl

H 2N

H

Rx-ID: 2727260 View in Reaxys 50/63 Yield

Conditions & References With NaPF6, (+)-(S,S)-Weinsaeure-di(5-nonyl)ester in dichloromethane, water, T= 4 °C , study of the separation of various α-aminoalcohol enantiomers with lipophilic anions by partition between aqueous and lipophilic phase containing esters of tartric acid, Product distribution Prelog, Vladimir; Stojanac, Zarko; Kovacevic, Krunoslav; Helvetica Chimica Acta; vol. 65; nb. 1; (1982); p. 377 384 View in Reaxys

N

Mg

H

OH

H 2N

I Si O

H

Rx-ID: 1671431 View in Reaxys 51/63

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

18/24

2016-04-27 15:52:06

Yield

Conditions & References With sodium tetrahydroborate, 1) Et2O, 12 h, room temperature, 2) THF, MeOH, -50 deg C, 4 h, Yield given. Multistep reaction Effenberger, Franz; Gutterer, Beate; Ziegler, Thomas; Liebigs Annalen der Chemie; nb. 3; (1991); p. 269 - 273 View in Reaxys

H

OH

H HO

NH 2

HO

H 2N

H

H N

Rx-ID: 2654231 View in Reaxys 52/63 Yield

Conditions & References With hydrogenchloride, sodium tetrahydroborate, ozone, Multistep reaction. Title compound not separated from byproducts Kashima, Choji; Maruyama, Tatsuya; Fujioka, Yoko; Harada, Kazuo; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1989); p. 1041 - 1046 View in Reaxys

H 2N

H

HO

H

H

OH

H 2N

H 2N

H

HO

H

H

racemate

Rx-ID: 2198545 View in Reaxys 53/63 Yield

Conditions & References Brown; Moudachirou; Tetrahedron; vol. 50; nb. 34; (1994); p. 10309 - 10320 View in Reaxys Schmid; Wirnsberger; Guebitz; Pharmazie; vol. 51; nb. 11; (1996); p. 852 - 854 View in Reaxys

H Si

–+

Br Mg

N Si

H

OH

HO

H 2N

NH 2 H

H

O O

Rx-ID: 2511253 View in Reaxys 54/63 Yield

Conditions & References Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Bonar-Law; Davis; Dorgan; Reetz; Wehrsig; Tetrahedron Letters; vol. 31; nb. 46; (1990); p. 6725 - 6728 View in Reaxys

O

HN

O

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

19/24

2016-04-27 15:52:06

H

OH

OH

O

OH

O

H 2N H

Rx-ID: 1551482 View in Reaxys 55/63 Yield

Conditions & References Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Narasaka, Koichi; Miwa, Tetsuo; Hayashi, Hiroki; Ohta, Masako; Chemistry Letters; (1984); p. 1399 - 1402 View in Reaxys

O

OH

OH

H

HN

OH

O

O

H 2N

O

H

Rx-ID: 2895478 View in Reaxys 56/63 Yield

Conditions & References Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Narasaka, Koichi; Miwa, Tetsuo; Hayashi, Hiroki; Ohta, Masako; Chemistry Letters; (1984); p. 1399 - 1402 View in Reaxys

H

HN

O

O

OH

OH

O

OH

O

H 2N H

Rx-ID: 2896839 View in Reaxys 57/63 Yield

Conditions & References Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Narasaka, Koichi; Miwa, Tetsuo; Hayashi, Hiroki; Ohta, Masako; Chemistry Letters; (1984); p. 1399 - 1402 View in Reaxys

H

HN

O

O

OH

OH

O

OH

H 2N O

H

Rx-ID: 3837998 View in Reaxys 58/63 Yield

Conditions & References Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Narasaka, Koichi; Miwa, Tetsuo; Hayashi, Hiroki; Ohta, Masako; Chemistry Letters; (1984); p. 1399 - 1402 View in Reaxys

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

20/24

2016-04-27 15:52:06

O

H

OH

palladium HO

OH

H 2N H

H N OH

Rx-ID: 7989523 View in Reaxys 59/63 Yield

Conditions & References Hydrogenation, isomer of mp: 71 degree Patent; I.G. Farbenind.; DE587586; (1930); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 20; p. 963 View in Reaxys

H

OH

HO

H

N

H

H

H

palladium

OH

H 2N H

O

Rx-ID: 7989522 View in Reaxys 60/63 Yield

Conditions & References eines Gemisches.Hydrogenation Patent; I.G. Farbenind.; DE587586; (1930); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 20; p. 963 View in Reaxys

H

OH

H 2N H

Rx-ID: 7363071 View in Reaxys 61/63 Yield 98%

Conditions & References 11 : EXAMPLE 11 STR36 EXAMPLE 11 STR36 Following the procedure described in Example 1 using 1,5-dibromopentane and (1R,2S)-norephedrine the titled compound was prepared in a 98percent yield.

1 H NMR (300 MHz, CDCl ) δ: 7.38-7.20 (m, 5H), 5.0 (d, 1H), 3.58 (s, br, 1H), 2.69 (m, 2H), 2.56 (m, 2H), 2.48 (m, 3 1H), 1.82 (m, 6H), 0.80 (d, 3H).

Patent; Merck and Co., Inc.; US5856492; (1999); (A1) English View in Reaxys

96%

15 : EXAMPLE 15 STR40 EXAMPLE 15 STR40 Following the procedure described in Example 1 using 1,3-dibromopropane and (1R,2S)-norephedrine the titled compound was prepared in a 96percent yield.

1 H NMR (300 MHz, CDCl ) δ: 7.34-7.15 (m, 5H), 7.43 (d, 1H), 3.48-3.20 (m, 4H), 2.47 (m, 1H), 2.37 (s, 1H), 2.08 3 (m, 2H), 0.64 (d, 3H).

Patent; Merck and Co., Inc.; US5856492; (1999); (A1) English View in Reaxys

96%

6 : EXAMPLE 6 EXAMPLE 6 The procedure was as in Example 4; but instead of the dioxane, there were employed 200 ml of tetrahydrofurane as solvent.

There were obtained 44.4 grams of the salt of S-(carboxymethyl)-(R)-cysteine and (1R,2S)-2-amino-1-phenyl-propan-1-ol, corresponding to a yield of 96percent.

The melting point was 60° C. and the rotation -38.8° (T=20° C.; c=1 in water).

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

21/24

2016-04-27 15:52:06

Patent; Degussa Aktiengesellschaft; US4416827; (1983); (A1) English View in Reaxys 93%

10 : EXAMPLE 10 STR35 EXAMPLE 10 STR35 Following the procedure described in Example 1 using α,α'-dibromo-o-xylene and (1R,2S)-norephedrine the titled compound was prepared in a 93percent yield.

1 H NMR (300 MHz, CDCl ) δ: 7.43-7.36 (m, 4H), 7.32-7.25 (m, 5H), 5.11 (d, 1H), 4.21 (d, 2H), 4.05 (d, 2H), 3.62 (s, 3 br, 1H), 2.90 (m, 1H), 0.95 (d, 3H).

Patent; Merck and Co., Inc.; US5856492; (1999); (A1) English View in Reaxys Hassner,A.; Burke,S.S.; Tetrahedron; vol. 30; (1974); p. 2613 - 2621 View in Reaxys Kalm,M.J.; Journal of Organic Chemistry; vol. 25; (1960); p. 1929 - 1937 View in Reaxys 1 : EXAMPLE 1 EXAMPLE 1 A mixture of 50 grams (0.28 mole) of S-(carboxymethyl)-(R)-cysteine and 42.5 grams (0.28 mole) of (1RS,2SR)-2amino-1-phenyl-propan-1-ol were dissolved in 50 ml of water.

The solution was held at 30° to 40° C. and treated dropwise with ethanol until crystalization began, then cooled slowly to 5° C. and filtered under suction.

The residue was washed with 150 ml of ethanol which contained 10percent of water and dried at 50° C. and 25 mbar.

The material recovered was the salt of S-(carboxymethyl)-(R)-cysteine and (1R,2S)-2-amino-1-phenyl-propan-1-ol.

The yield was 44.8 grams, corresponding to 97percent based on the (1R,2S)-2-amino-1-phenyl-propan-1-ol contained in the racemate employed.

The melting point of the salt recovered was 66° C. and the specific rotation -37.2° (T=20° C.; c=1 in water).

The salt was dissolved in 150 ml of water and the solution adjusted to pH 2.8 by means of 2 N aqueous sulfuric acid at 25° C. Hereby, the S-(carboxymethyl)-(R)-cysteine was precipitated.

It was filtered off.

The filtrate was treated with 200 ml of a 50percent aqueous sodium hydroxide solution.

The mixture was extracted three times, each time with 100 ml of methylene chloride.

The combined extracts were dried with sodium sulfate.

Then the methylene chloride was driven off and the residue recrystallized in methyl tert. butyl ether.

There were obtained 19.6 grams of (1R,2S)-2-amino-1-phenyl-propan-1-ol, corresponding to a yield of 95percent based on the (1R,2S)-2-amino-1-phenyl-propan-1-ol contained in the racemate employed.

Patent; Degussa Aktiengesellschaft; US4416827; (1983); (A1) English View in Reaxys 1 : (-)-Norephedrine EXAMPLE 1 (-)-Norephedrine 250 grams of (+-)-norephedrine were stirred with 206 grams of (+)-ψ-N-(1-methyl-2-phenyl-2-hydroxyethyl)-maleic acid monoamide (Abbreviation: (+)-ψ-NEMA) in 2.28 liters of methyl ethyl ketone for 6 hours at an interval temperature of 10°-120° C. Then there was filtered off with suction the precipitated (+)-ψ-NEMA salt of the (-)-norephedrine.

After washing with acetone it was dried at 60° C. in a vacuum.

Yield: 309.8 grams=93.6percent of theory; M.P. 148°-150° C. [α]D 20 (2.5percent in 96percent ethanol): -63.4°.

Patent; Deutsche Gold- und Silber-Scheideanstalt vormals Roessler; US4226803; (1980); (A1) English View in Reaxys 4 : Example 4 Example 4 L-erythro-(1R,2S)-2-amino-1-phenylpropan-1-ol A mixture of L-(R)-phenylacetylcarbinol (purity 68.3percent; 65.95 g, 300 mmol), benzylamine (36.82 g, 343 mmol), recovered 5percent Pd/C (3.60 g) and methanol (139 ml) was stirred for 4 hours at 5°C under hydrogen atmosphere (9 kg/cm2).

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

22/24

2016-04-27 15:52:06

Subsequently, fresh 5percent Pd/C (8.70 g, water content: 53.4percent) was added to the mixture, the reaction temperature was raised to 60°C, and the mixture was stirred for 2 hours and one quarter.

The reaction mixture was filtered and the residue was washed with methanol (20 ml).

The filtrate and the washed liquor were combined to obtain a methanol solution (231.70 g) of L-erythro-(1R,2S)-2amino-1-phenylpropan-1-ol.

Erythro:threo = 92.75:7.25 (conditions for GLC analysis are the same as in Example 3); Patent; NAGASE and COMPANY, LTD.; EP1142864; (2001); (A1) English View in Reaxys

H

salt of S-(carboxymethyl)-(R)-cysteine

OH

H 2N H

Rx-ID: 25093894 View in Reaxys 62/63 Yield 90%

Conditions & References 2 : EXAMPLE 2 EXAMPLE 2 50 grams (0.28 mole) of S-(carboxymethyl)-(R)-cysteine were suspended in 400 ml of ethanol which contained 10percent of water.

To this suspension there were added 42.5 grams (0.28 mole) of (1RS,2SR)-2-amino-1-phenyl-propan-1-ol.

The mixture was held at that time at 40° to 50° C. and then for one hour under reflux at the boiling point, then cooled to 23° C. in the course of 30 minutes and filtered under suction.

The residue was washed with 200 ml of methanol and dried at 50° C. and 25 mbar.

There were obtained 41.6 grams of the salt of S-(carboxymethyl)-(R)-cysteine and (1R,2S)-2-amino-1-phenyl-propan-1-ol*) The melting point was 68° C. and the specific rotation -38.2° (T=20° C.; c=1 in water). *) corresponding to a yield of 90percent based on the (1R,2S)-2-amino- 1-phenyl-propan-1-ol in the racemate added.

Patent; Degussa Aktiengesellschaft; US4416827; (1983); (A1) English View in Reaxys

81%

7 : EXAMPLE 7 EXAMPLE 7 The procedure was as in Example B1, except the S-(carboxymethyl)-(RS)-cysteine was suspended in 100 ml of water, to this suspension there was added the (1R,2S)-2-amino-1-phenyl-propan-1-ol, the suspension warmed to 60° C. and evaporated under reduced pressure to 105 grams and the residue taken up in 800 ml of boiling methanol.

There were obtained 37.4 grams, corresponding to 81percent yield, of the salt of S-(carboxymethyl)-(R)-cysteine and (1R,2S)-2-amino-1-phenyl-propan-1-ol.

The melting point was 68° C. and the rotation -38.1° (c=1 in water).

Patent; Degussa Aktiengesellschaft; US4416828; (1983); (A1) English View in Reaxys

80%

2 : EXAMPLE 2 EXAMPLE 2 The procedure was as in Example B1, but the starting materials were suspended in 1000 ml of water free methanol, and the suspension was held for 2 hours under stirring at 50° C. to 60° C. There were obtained 37.0 grams, corresponding to 80percent yield of the salt of S-(carboxymethyl)-(R)-cysteine and (1R,2S)-2-amino-1-phenyl-propan-1-ol.

The melting point of the salt was 68° C. and the rotation -38.3° (c=1 in water).

Patent; Degussa Aktiengesellschaft; US4416828; (1983); (A1) English View in Reaxys

78%

4 : EXAMPLE 4 EXAMPLE 4 The procedure was as in Example 1, but the starting materials were suspended in 800 ml of dioxane and there was supplied water to this suspension at the boiling point until all materials were dissolved.

The solution was cooled in the course of 2 hours to 18° C. There were obtained 36.1 grams, corresponding to 78percent yield of the salt of S-(carboxymethyl)-(R)-cysteine and (1R,2S)-2-amino-1-phenyl-propan-1-ol.

The melting point was 68° C. and the rotation -37.4° (T=20° C.; c=1 in water).

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

23/24

2016-04-27 15:52:06

Patent; Degussa Aktiengesellschaft; US4416827; (1983); (A1) English View in Reaxys 78%

4 : EXAMPLE 4 EXAMPLE 4 The procedure was as in Example B1, but the starting materials were suspended in dioxane, and there was supplied water to this suspension at the boiling point until all materials were dissolved.

The solution was cooled in the course of 2 hours to 25° C. There were obtained 36.0 grams, corresponding to 78percent yield of the salt of S-(carboxymethyl)-(R)-cysteine and (1R,2S)-2-amino-1-phenyl-propan-1-ol.

The melting point was 68° C. and the rotation -37.4° (c=1 in water).

Patent; Degussa Aktiengesellschaft; US4416828; (1983); (A1) English View in Reaxys

H

OH

HO

H 2N H

H 2N

Cl

H

Rx-ID: 25391002 View in Reaxys 63/63 Yield 73.4%

Conditions & References 2 : (-)-Norephedrine The thus obtained 9.7 grams of the (-)-norephedrine salt were suspended in 75 ml of water, 2.2 ml of concentrated hydrochloric acid added and the mixture stirred a further 15 minutes.

The precipitated (+)-NEMA was filtered off with suction, washed with water and dried at 60° C. Yield: 5.7 grams=94.6percent of theory.

To isolate the (-)-norephedrine the aqueous filtrate was evaporated in a vacuum, the residue stirred with acetone and the crude hydrochloride filtered off with suction.

By recrystallization from isopropanol there were obtained 3.3 grams of (-)-norephedrine hydrochloride.

Yield 73.4percent of theory; M.P. 166°-171° C. [α]D 20 (5percent in water): -32.3°.

Patent; Deutsche Gold- und Silber-Scheideanstalt vormals Roessler; US4226803; (1980); (A1) English View in Reaxys

Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

24/24

2016-04-27 15:52:06