1R,2R)-(−)-Norpseudoephedrine hydrochloride [CAS 53643-20-2; InChIKey DYWNLSQWJMTVGJ-JXLXBRS

Query 1. Query

Query

Results

Date

RX.PXRN=2207679

39 reactions in Reaxys

2016-04-27 18h:34m:49s (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.

1/15

2016-04-27 18:35:30

H

OH

H

H 2N HO

OH

H 2N H

H

H

N OH

Rx-ID: 28350948 View in Reaxys 1/39 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 Patent; Emmellen Biotech Pharmaceuticals Limited; US2009/112025; (2009); (A1) English View in Reaxys

H N

O

OH

H

OH

H 2N H

O

Rx-ID: 33637695 View in Reaxys 2/39 Yield

Conditions & References

79.4 %

With trifluoroacetic acid in dichloromethane, T= 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

H 2N

H

HO

H

H

OH

H 2N H

Rx-ID: 12145820 View in Reaxys 3/39 Yield

Conditions & References Reaction Steps: 3 1: triethylamine / tetrahydrofuran / 2 h / 20 °C 2: triethylamine / tetrahydrofuran / 3 h / 48 °C 3: 1.792 g / LiOH / H2O / 0.5 h / 85 °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.

2/15

2016-04-27 18:35:30

With lithium hydroxide, triethylamine in tetrahydrofuran, water Groeper, Jonathan A.; Hitchcock, Shawn R.; Ferrence, Gregory M.; Tetrahedron Asymmetry; vol. 17; nb. 20; (2006); p. 2884 - 2889 View in Reaxys Reaction Steps: 2 1.1: toluene 1.2: HCl / toluene 2.1: aq. HCl / toluene With hydrogenchloride in toluene Shah, Shrenik K.; Chen, Natalie; Guthikonda, Ravindra N.; Mills, Sander G.; Malkowitz, Lorraine; Springer, Martin S.; Gould, Sandra L.; DeMartino, Julie A.; Carella, Anthony; Carver, Gwen; Holmes, Karen; Schleif, William A.; Danzeisen, Renee; Hazuda, Daria; Kessler, Joseph; Lineberger, Janet; Miller, Michael; Emini, Emilio A.; MacCoss, Malcolm; Bioorganic and Medicinal Chemistry Letters; vol. 15; nb. 4; (2005); p. 977 - 982 View in Reaxys Reaction Steps: 3 1.1: pyridine / 16 h / 20 °C 2.1: sodium hydroxide / methanol; H2O / 0.5 h / 20 °C 3.1: thionyl chloride / 0.25 h / 0 °C 3.2: 86 mg / hydrochloric acid / H2O / 3 h / 100 °C With pyridine, sodium hydroxide, thionyl chloride in methanol, water Ishida, Keishi; Matsuda, Hisashi; Okita, Yuji; Murakami, Masahiro; Tetrahedron; vol. 58; nb. 38; (2002); p. 7645 - 7652 View in Reaxys Reaction Steps: 3 1: triethylamine / tetrahydrofuran / 2.08 h / 0 - 20 °C / |Inert atmosphere 2: triethylamine / tetrahydrofuran / 6 h / 0 - 49 °C / |Inert atmosphere 3: lithium hydroxide hydrate / tetrahydrofuran; water / 1.75 h / 60 - 90 °C / |Inert atmosphere With triethylamine, lithium hydroxide hydrate in tetrahydrofuran, water Tan, Darlene Q.; Younai, Ashkaan; Pattawong, Ommidala; Fettinger, James C.; Cheong, Paul Ha-Yeon; Shaw, Jared T.; Organic Letters; vol. 15; nb. 19; (2013); p. 5126 - 5129 View in Reaxys

H

HO Cl

H 2N

H

OH

H 2N H

Rx-ID: 28240995 View in Reaxys 4/39 Yield

Conditions & References

70 %

With sodium hydroxide in diethyl ether, water Denmark, Scott E.; Ares, Jeffrey J.; Journal of Organic Chemistry; vol. 73; nb. 24; (2008); p. 9647 - 9656 View in Reaxys

O O NH

H

OH

H 2N H

O Si

Rx-ID: 36649148 View in Reaxys 5/39 Yield 0.5 g

Conditions & References With lithium hydroxide hydrate in tetrahydrofuran, water, Time= 1.75h, T= 60 - 90 °C , Inert atmosphere

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.

3/15

2016-04-27 18:35:30

Tan, Darlene Q.; Younai, Ashkaan; Pattawong, Ommidala; Fettinger, James C.; Cheong, Paul Ha-Yeon; Shaw, Jared T.; Organic Letters; vol. 15; nb. 19; (2013); p. 5126 - 5129 View in Reaxys

H N

O

OH

H

OH

H 2N H

O

Rx-ID: 12151751 View in Reaxys 6/39 Yield

Conditions & References Reaction Steps: 2 1: triethylamine / tetrahydrofuran / 3 h / 48 °C 2: 1.792 g / LiOH / H2O / 0.5 h / 85 °C With lithium hydroxide, triethylamine in tetrahydrofuran, water Groeper, Jonathan A.; Hitchcock, Shawn R.; Ferrence, Gregory M.; Tetrahedron Asymmetry; vol. 17; nb. 20; (2006); p. 2884 - 2889 View in Reaxys Reaction Steps: 2 1: triethylamine / tetrahydrofuran / 6 h / 0 - 49 °C / |Inert atmosphere 2: lithium hydroxide hydrate / tetrahydrofuran; water / 1.75 h / 60 - 90 °C / |Inert atmosphere With triethylamine, lithium hydroxide hydrate in tetrahydrofuran, water Tan, Darlene Q.; Younai, Ashkaan; Pattawong, Ommidala; Fettinger, James C.; Cheong, Paul Ha-Yeon; Shaw, Jared T.; Organic Letters; vol. 15; nb. 19; (2013); p. 5126 - 5129 View in Reaxys

H

O

H

OH

HO

H 2N

E

NH 2 H

H

Cl

Rx-ID: 9015462 View in Reaxys 7/39 Yield

Conditions & References Stage 1: With pyridine 1-oxide, silver tetrafluoroborate, [(R,R)-1,2-(N=CHC6H4O-o)2-cyclohexane]MnN in dichloromethane, Time= 48h, T= 0 °C Stage 2: With hydrogenchloride in water, Time= 30h, Heating, Further stages. Title compound not separated from byproducts.

Nishimura, Masaaki; Minakata, Satoshi; Takahashi, Toru; Oderaotoshi, Yoji; Komatsu, Mitsuo; Journal of Organic Chemistry; vol. 67; nb. 7; (2002); p. 2101 - 2110 View in Reaxys

O

H N

H

OH

H

OH

H 2N

H

H

Rx-ID: 9250482 View in Reaxys 8/39 Yield 86 mg

Conditions & References Stage 1: With thionyl chloride, Time= 0.25h, T= 0 °C Stage 2: With hydrogenchloride in water, Time= 3h, T= 100 °C Ishida, Keishi; Matsuda, Hisashi; Okita, Yuji; Murakami, Masahiro; Tetrahedron; vol. 58; nb. 38; (2002); p. 7645 - 7652 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.

4/15

2016-04-27 18:35:30

H

OH

H 2N HO

H

H

O

Rx-ID: 35891577 View in Reaxys 9/39 Yield

Conditions & References With (R)-alanine, pyridoxal 5'-phosphate, Aspergillus terreus ω-transaminase, Thiamine pyrophosphate, Adenineflavine dinucleotide, magnesium chloride in aq. buffer, T= 25 °C , pH= 7.5, Enzymatic reaction, Reagent/catalyst 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 (R)-alanine, (R)-selective-ω-transaminase from Aspergillus terreus in aq. buffer, Time= 12h, T= 25 °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

OH

H

E N

OH

H 2N

H

OH

H 2N H

H

OH

Rx-ID: 23597159 View in Reaxys 10/39 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

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.

5/15

2016-04-27 18:35:30

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 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 H 2N

H

HN O O

Rx-ID: 10383866 View in Reaxys 11/39 Yield

Conditions & References

1.792 g

With lithium hydroxide in water, Time= 0.5h, T= 85 °C Groeper, Jonathan A.; Hitchcock, Shawn R.; Ferrence, Gregory M.; Tetrahedron Asymmetry; vol. 17; nb. 20; (2006); p. 2884 - 2889 View in Reaxys

O H 2N

H

OH

H 2N

H

OH

H 2N H

H

Rx-ID: 38002607 View in Reaxys 12/39 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

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.

6/15

2016-04-27 18:35:30

H

OH

H 2N HO

H

H

H 2N

O

Rx-ID: 38002574 View in Reaxys 13/39 Yield

Conditions & References With (R)-alanine, (R)-selective-ω-transaminase from Aspergillus terreus in aq. buffer, Time= 12h, T= 25 °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

OH O

OH

H

NE

H 2N

H

OH

H 2N H

H

Rx-ID: 4742198 View in Reaxys 14/39 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

OH

H H 2N

H

N O

Rx-ID: 9821189 View in Reaxys 15/39 Yield

Conditions & References With hydrogenchloride in toluene Shah, Shrenik K.; Chen, Natalie; Guthikonda, Ravindra N.; Mills, Sander G.; Malkowitz, Lorraine; Springer, Martin S.; Gould, Sandra L.; DeMartino, Julie A.; Carella, Anthony; Carver, Gwen; Holmes, Karen; Schleif, William A.; Danzeisen, Renee; Hazuda, Daria; Kessler, Joseph; Lineberger, Janet; Miller, Michael; Emini, Emilio A.; MacCoss, Malcolm; Bioorganic and Medicinal Chemistry Letters; vol. 15; nb. 4; (2005); p. 977 - 982 View in Reaxys

O H

O

OH

H 2N

HN

H

O

Rx-ID: 14450064 View in Reaxys 16/39 Yield

Conditions & References Reaction Steps: 2

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.

7/15

2016-04-27 18:35:30

1.1: sodium hydroxide / methanol; H2O / 0.5 h / 20 °C 2.1: thionyl chloride / 0.25 h / 0 °C 2.2: 86 mg / hydrochloric acid / H2O / 3 h / 100 °C With sodium hydroxide, thionyl chloride in methanol, water Ishida, Keishi; Matsuda, Hisashi; Okita, Yuji; Murakami, Masahiro; Tetrahedron; vol. 58; nb. 38; (2002); p. 7645 - 7652 View in Reaxys

OH

H H 2N

E

H

Rx-ID: 15000392 View in Reaxys 17/39 Yield

Conditions & References Reaction Steps: 2 1: AgBF4; pyridine N-oxide; (S,S)-nitridomanganese complex / CH2Cl2 2: aq. HCl / 30 h / Heating With pyridine 1-oxide, hydrogenchloride, silver tetrafluoroborate, (S,S)-nitridomanganese in dichloromethane Minakata, Satoshi; Nishimura, Masaaki; Takahashi, Toru; Oderaotoshi, Yoji; Komatsu, Mitsuo; Tetrahedron Letters; vol. 42; nb. 51; (2001); p. 9019 - 9022 View in Reaxys

O HO

H

NE

OH

H 2N H

Rx-ID: 17199959 View in Reaxys 18/39 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: 17233209 View in Reaxys 19/39 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.

8/15

2016-04-27 18:35:30

O

H

OH

H 2N

O

H

Rx-ID: 17238838 View in Reaxys 20/39 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

H

OH

H 2N HO

H

H

O

Rx-ID: 33637684 View in Reaxys 21/39 Yield

Conditions & References Reaction Steps: 7 1.1: amidosulfonyl chloride / N,N-dimethyl acetamide / 1 h / 20 °C 2.1: toluene-4-sulfonic acid / toluene / 0.5 h / Reflux 3.1: formic acid; Rh-(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine; triethylamine / ethyl acetate / 0.25 h / 20 °C 4.1: 4-(N,N-dimethlyamino)pyridine / dichloromethane / 0.17 h / 20 °C 5.1: cesium fluoride / N,N-dimethyl-formamide / 12 h / 60 °C 5.2: 1 h / 20 °C 6.1: potassium cyanide / methanol / 4 h / 65 °C 7.1: trifluoroacetic acid / dichloromethane / 20 °C With 4-(N,N-dimethlyamino)pyridine, potassium cyanide, formic acid, Rh-(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine, amidosulfonyl chloride, toluene-4-sulfonic acid, triethylamine, cesium fluoride, trifluoroacetic acid in methanol, dichloromethane, N,N-dimethyl acetamide, ethyl acetate, N,N-dimethyl-formamide, toluene Lee, Hyeon-Kyu; Kang, Soyeong; Choi, Eun Bok; Journal of Organic Chemistry; vol. 77; nb. 12; (2012); p. 5454 5460 View in Reaxys Reaction Steps: 3 1: (S)-1-phenyl-ethylamine; Chromobacterium violaceum ω-transaminase; pyridoxal 5'-phosphate / aq. buffer / 16 h / 20 °C / pH 7.5 / |Enzymatic reaction 2: 2-oxo-propionic acid; Thiamine pyrophosphate; Adenine-flavine dinucleotide; magnesium chloride; Chromobacterium violaceum ω-transaminase; pyridoxal 5'-phosphate / aq. buffer / 24 h / 20 °C / pH 7.5 / |Enzymatic reaction 3: Thiamine pyrophosphate; Adenine-flavine dinucleotide; magnesium chloride; Aspergillus terreus ω-transaminase; (R)-alanine; pyridoxal 5'-phosphate / aq. buffer / 25 °C / pH 7.5 / |Enzymatic reaction With (R)-alanine, (S)-1-phenyl-ethylamine, pyridoxal 5'-phosphate, Aspergillus terreus ω-transaminase, Chromobacterium violaceum ω-transaminase, Thiamine pyrophosphate, 2-oxo-propionic acid, Adenine-flavine dinucleotide, magnesium chloride in aq. buffer 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

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.

9/15

2016-04-27 18:35:30

H

H

OH

H 2N H

O

Rx-ID: 38002580 View in Reaxys 22/39 Yield

Conditions & References Reaction Steps: 2 1: AHAS-I from E.coli / aq. buffer / 1.5 h / 25 °C / |Enzymatic reaction 2: (R)-alanine; (R)-selective-ω-transaminase from Aspergillus terreus / aq. buffer / 12 h / 25 °C / |Enzymatic reaction With (R)-alanine, (R)-selective-ω-transaminase from Aspergillus terreus, AHAS-I from E.coli 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: (R)-alanine; (R)-selective-ω-transaminase from Aspergillus terreus / aq. buffer / 12 h / 25 °C / |Enzymatic reaction With (R)-alanine, (R)-selective-ω-transaminase from Aspergillus terreus, (S)-selective carboligase ApPDC variant E469G 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

O O

O S

H

O H

N H

O

OH

H 2N H

Rx-ID: 33637608 View in Reaxys 23/39 Yield

Conditions & References Reaction Steps: 3 1.1: cesium fluoride / N,N-dimethyl-formamide / 12 h / 60 °C 1.2: 1 h / 20 °C 2.1: potassium cyanide / methanol / 4 h / 65 °C 3.1: trifluoroacetic acid / dichloromethane / 20 °C With potassium cyanide, cesium fluoride, trifluoroacetic acid in methanol, dichloromethane, N,N-dimethyl-formamide 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

O

HN

H

O

OH

H 2N H

Rx-ID: 33637613 View in Reaxys 24/39 Yield

Conditions & References Reaction Steps: 2 1: potassium cyanide / methanol / 4 h / 65 °C 2: trifluoroacetic acid / dichloromethane / 20 °C With potassium cyanide, trifluoroacetic acid in methanol, dichloromethane

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.

10/15

2016-04-27 18:35:30

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

S

N

Cl

OH

H

O

H 2N H

Rx-ID: 33637623 View in Reaxys 25/39 Yield

Conditions & References Reaction Steps: 6 1.1: toluene-4-sulfonic acid / toluene / 0.5 h / Reflux 2.1: formic acid; Rh-(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine; triethylamine / ethyl acetate / 0.25 h / 20 °C 3.1: 4-(N,N-dimethlyamino)pyridine / dichloromethane / 0.17 h / 20 °C 4.1: cesium fluoride / N,N-dimethyl-formamide / 12 h / 60 °C 4.2: 1 h / 20 °C 5.1: potassium cyanide / methanol / 4 h / 65 °C 6.1: trifluoroacetic acid / dichloromethane / 20 °C With 4-(N,N-dimethlyamino)pyridine, potassium cyanide, formic acid, Rh-(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine, toluene-4-sulfonic acid, triethylamine, cesium fluoride, trifluoroacetic acid in methanol, dichloromethane, ethyl acetate, N,N-dimethyl-formamide, 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

H

OH

H 2N H

Rx-ID: 33637639 View in Reaxys 26/39 Yield

Conditions & References Reaction Steps: 5 1.1: formic acid; Rh-(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine; triethylamine / ethyl acetate / 0.25 h / 20 °C 2.1: 4-(N,N-dimethlyamino)pyridine / dichloromethane / 0.17 h / 20 °C 3.1: cesium fluoride / N,N-dimethyl-formamide / 12 h / 60 °C 3.2: 1 h / 20 °C 4.1: potassium cyanide / methanol / 4 h / 65 °C 5.1: trifluoroacetic acid / dichloromethane / 20 °C With 4-(N,N-dimethlyamino)pyridine, potassium cyanide, formic acid, Rh-(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine, triethylamine, cesium fluoride, trifluoroacetic acid in methanol, dichloromethane, ethyl acetate, N,Ndimethyl-formamide 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 H

O S

NH H

H

OH

H 2N H

Rx-ID: 33637651 View in Reaxys 27/39

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.

11/15

2016-04-27 18:35:30

Yield

Conditions & References Reaction Steps: 4 1.1: 4-(N,N-dimethlyamino)pyridine / dichloromethane / 0.17 h / 20 °C 2.1: cesium fluoride / N,N-dimethyl-formamide / 12 h / 60 °C 2.2: 1 h / 20 °C 3.1: potassium cyanide / methanol / 4 h / 65 °C 4.1: trifluoroacetic acid / dichloromethane / 20 °C With 4-(N,N-dimethlyamino)pyridine, potassium cyanide, cesium fluoride, trifluoroacetic acid in methanol, dichloromethane, N,N-dimethyl-formamide 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: 33637670 View in Reaxys 28/39 Yield

Conditions & References Reaction Steps: 8 1.1: diethyl ether / 4 h / Reflux 2.1: amidosulfonyl chloride / N,N-dimethyl acetamide / 1 h / 20 °C 3.1: toluene-4-sulfonic acid / toluene / 0.5 h / Reflux 4.1: formic acid; Rh-(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine; triethylamine / ethyl acetate / 0.25 h / 20 °C 5.1: 4-(N,N-dimethlyamino)pyridine / dichloromethane / 0.17 h / 20 °C 6.1: cesium fluoride / N,N-dimethyl-formamide / 12 h / 60 °C 6.2: 1 h / 20 °C 7.1: potassium cyanide / methanol / 4 h / 65 °C 8.1: trifluoroacetic acid / dichloromethane / 20 °C With 4-(N,N-dimethlyamino)pyridine, potassium cyanide, formic acid, diethyl ether, Rh-(S,S)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine, amidosulfonyl chloride, toluene-4-sulfonic acid, triethylamine, cesium fluoride, trifluoroacetic acid in methanol, dichloromethane, N,N-dimethyl acetamide, ethyl acetate, N,N-dimethyl-formamide, 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

H

OH

H 2N H

H

Rx-ID: 35891581 View in Reaxys 29/39 Yield

Conditions & References Reaction Steps: 2 1: 2-oxo-propionic acid; Thiamine pyrophosphate; Adenine-flavine dinucleotide; magnesium chloride; Chromobacterium violaceum ω-transaminase; pyridoxal 5'-phosphate / aq. buffer / 24 h / 20 °C / pH 7.5 / |Enzymatic reaction 2: Thiamine pyrophosphate; Adenine-flavine dinucleotide; magnesium chloride; Aspergillus terreus ω-transaminase; (R)-alanine; pyridoxal 5'-phosphate / aq. buffer / 25 °C / pH 7.5 / |Enzymatic reaction With (R)-alanine, pyridoxal 5'-phosphate, Aspergillus terreus ω-transaminase, Chromobacterium violaceum ω-transaminase, Thiamine pyrophosphate, 2-oxo-propionic acid, Adenine-flavine dinucleotide, magnesium chloride in aq. buffer 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

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.

12/15

2016-04-27 18:35:30

OH

H

H H 2N

H

O

H 2N

Rx-ID: 38002577 View in Reaxys 30/39 Yield

Conditions & References Reaction Steps: 2 1: AHAS-I from E.coli / aq. buffer / 1.5 h / 25 °C / |Enzymatic reaction 2: (R)-alanine; (R)-selective-ω-transaminase from Aspergillus terreus / aq. buffer / 12 h / 25 °C / |Enzymatic reaction With (R)-alanine, (R)-selective-ω-transaminase from Aspergillus terreus, AHAS-I from E.coli 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: (R)-alanine; (R)-selective-ω-transaminase from Aspergillus terreus / aq. buffer / 12 h / 25 °C / |Enzymatic reaction With (R)-alanine, (R)-selective-ω-transaminase from Aspergillus terreus, (S)-selective carboligase ApPDC variant E469G 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

O

H

EN

OH

H 2N

O

H

OH

H

H HO

H 2N

NH 2 H

H 2N

H

HO

H

H

Rx-ID: 5029024 View in Reaxys 31/39 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 View in Reaxys

H

H

HO

OH

H 2N

O

O

O

H

H 2N

Rx-ID: 35891578 View in Reaxys 32/39 Yield

Conditions & References With (R)-alanine, pyridoxal 5'-phosphate, Aspergillus terreus ω-transaminase, E. coli acetohydroxyacid synthase I, Thiamine pyrophosphate, Adenine-flavine dinucleotide, magnesium chloride in aq. buffer, pH= 7.5, Enzymatic reaction 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

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.

13/15

2016-04-27 18:35:30

OH

H H 2N

N O

H

Rx-ID: 9027334 View in Reaxys 33/39 Yield

Conditions & References With hydrogenchloride, Time= 30h, Heating Minakata, Satoshi; Nishimura, Masaaki; Takahashi, Toru; Oderaotoshi, Yoji; Komatsu, Mitsuo; Tetrahedron Letters; vol. 42; nb. 51; (2001); p. 9019 - 9022 View in Reaxys

H

(1R,2R)-1-phenyl-2-phthalimido-propan-1-ol

OH

H 2N H

Rx-ID: 7363076 View in Reaxys 34/39 Yield

Conditions & References With ethanol, hydrazine hydrate Fles; Markovac-Prpic; Croatica Chemica Acta; vol. 29; (1957); p. 183,185 View in Reaxys

O

OH

H

H

NH 2

HO

OH

H

H

OH

H 2N H

racemate

Rx-ID: 383131 View in Reaxys 35/39 Yield

Conditions & References Jarowski; Hartung; Journal of Organic Chemistry; vol. 8; (1943); p. 564,566 View in Reaxys

HO

H

threo H 2N

Cl

H

OH

H 2N

threo

H

Rx-ID: 2727263 View in Reaxys 36/39 Yield

Conditions & References Prelog, Vladimir; Mutak, Stjepan; Helvetica Chimica Acta; vol. 66; nb. 7; (1983); p. 2274 - 2278 View in Reaxys

H

O

O

N

Cl

O

H

H

NH 2

H

concentrated hydrochloric acid

OH

H 2N H

O

Rx-ID: 8469997 View in Reaxys 37/39 Yield

Conditions & References Nagai; Kanao; Justus Liebigs Annalen der Chemie; vol. 470; (1929); p. 174; Chem. Zentralbl.; vol. 99; nb. II; (1928); p. 2553

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.

14/15

2016-04-27 18:35:30

View in Reaxys Kanao; Yakugaku Zasshi; vol. 48; (1928); p. 145; Chem. Zentralbl.; vol. 100; nb. I; (1929); p. 748,749 View in Reaxys

O HO

H

OH

HO

NH 2

H

H

OH

O

OH

H

H

OH

H 2N H

racemate

Rx-ID: 204886 View in Reaxys 38/39 Yield

Conditions & References Nagai; Kanao; Justus Liebigs Annalen der Chemie; vol. 470; (1929); p. 174; Chem. Zentralbl.; vol. 99; nb. II; (1928); p. 2553 View in Reaxys Kanao; Yakugaku Zasshi; vol. 48; (1928); p. 145; Chem. Zentralbl.; vol. 100; nb. I; (1929); p. 748,749 View in Reaxys

H

OH

H 2N H

Rx-ID: 7363075 View in Reaxys 39/39 Yield

Conditions & References 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 Mueller et al.; Journal fuer Praktische Chemie (Leipzig); vol. 317; (1975); p. 153,154,155,157,158 View in Reaxys Each of the following compounds exhibited a significant dose- and time-effect, with an interaction of dose and time (all Fs>2.7; all p values <0.01): (+)-amphetamine, (-)-ephedrine, (+)-ephedrine, (-)-norpseudoephedrine, (+)-norpseudoephedrine and mephentermine.

Patent; Booth, Anthony; Caffrey, James L.; US2003/105332; (2003); (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.

15/15

2016-04-27 18:35:30