Ethanol → (2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride

HRID 1641640Notes

Reaction equation

HRID 1641640 reaction equation
[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9][C@@H:10]([CH3:14])[C:11]([OH:13])=[O:12])=[CH:3][CH:2]=1.S(Cl)([Cl:31])=O.[CH2:33](O)[CH3:34]>>[ClH:31].[CH2:33]([O:13][C:11](=[O:12])[C@H:10]([CH3:14])[CH2:9][C@H:8]([NH2:15])[CH2:7][C:4]1[CH:5]=[CH:6][C:1]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[CH:2][CH:3]=1)[CH3:34].[C:1]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:9][C@@H:10]([CH3:14])[C:11]([OH:13])=[O:12])=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 24386Thionyl ChlorideHCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid

Product 2

HCID 25017086(2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochlorideHCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid

Conditions

Temperature
65 °C

Procedure

150 g (2R,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid (3-a, R1=BOC, R2=R3=H) are added to 1500 ml ethanol at room temperature. The mixture is then warmed to an internal temperature of 60-70° C. 42.8 ml Thionyl chloride is then added over a period of 1 h to the reaction mixture. The mixture is then stirred for a further 2 h. 810 ml of the solvent is removed by distillation under reduced pressure. 1460 ml Heptane fraction is then added. 1310 ml of solvent is then removed by distillation under reduced pressure. 1460 ml Heptane fraction is then added. 520 ml of solvent is then removed by distillation under reduced pressure. 1460 ml Heptane fraction is then added. The mixture is then cooled to room temperature over a period of 1 h. The mixture is then stirred at room temperature for 2 h. The solid is then collected by filtration. The solid is then washed with heptane fraction (600 ml) and dried to give (2R,4S)-4-amino-5-biphenyl-4-yl-2-methylpentanoic acid ethyl ester hydrochloride (3-a, R1=R2=H, R3=Et). Spectroscopic data as given in Example 9-1 Method 1.

Workup

  1. custom810 ml of the solvent is removed by distillation under reduced pressure
  2. addition1460 ml Heptane fraction is then added
  3. custom1310 ml of solvent is then removed by distillation under reduced pressure
  4. addition1460 ml Heptane fraction is then added
  5. custom520 ml of solvent is then removed by distillation under reduced pressure
  6. addition1460 ml Heptane fraction is then added
  7. temperatureThe mixture is then cooled to room temperature over a period of 1 h
  8. stirringThe mixture is then stirred at room temperature for 2 h
  9. filtrationThe solid is then collected by filtration
  10. washThe solid is then washed with heptane fraction (600 ml)
  11. customdried

Sources & evidence

ORD record
ord-61ee8bb0358c4407b75d4817684a271e
Source dataset
uspto-grants-2012_02
Patent number
US08115016B2

Reaction notes

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