Ethanol → (2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid

HRID 1021059Notes

Reaction equation

HRID 1021059 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:29](=[O:33])(=[O:32])([OH:31])[OH:30].[CH2:34](O)[CH3:35]>>[S:29]([OH:33])([OH:32])(=[O:31])=[O:30].[CH2:34]([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)[CH3:35].[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 1118Sulfuric AcidHCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid

Product 2

HCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acidHCID 66739342HCID 66739342, compound

Conditions

Temperature
65 °C

Procedure

10 g (2R,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid (3-a, R1=BOC, R2=R3=H) are added to ethanol (100 ml). The mixture is heated to 65° C. 2 ml of concentrated sulphuric acid is then added over 0.5 h. The mixture is then stirred overnight. The ethanol is removed and heptane added. Further azeotropic distillations are performed using heptane to remove any residual ethanol. The solvent is removed in vacuo to afford (2R,4S)-4-amino-5-biphenyl-4-yl-2-methylpentanoic acid ethyl ester hydrogen sulphate (3-a, R1=R2=H, R3=Et). 1H NMR (DMSO): 1.12 (6H), 1.56 (1H), 1.87 (1H), 2.67 (1H), 2.78 (1H), 2.98 (1H), 3.76 (2H), 7.34 (3H), 7.47 (2H), 7.64 (4H), 8.57 m/z (ES+) 312 ([MH]+, 100.

Workup

  1. customThe ethanol is removed
  2. additionheptane added
  3. customto remove any residual ethanol
  4. customThe solvent is removed in vacuo

Sources & evidence

ORD record
ord-7b7fa01dcbfb4d07ab1d399eed03ef00
Source dataset
uspto-grants-2014_05
Patent number
US08716495B2

Reaction notes

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