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

HRID 1021058Notes

Reaction equation

HRID 1021058 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(Br)([Br:31])=O.[CH2:33](O)[CH3:34]>>[BrH: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 68176Thionyl bromideHCID 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 667388471038924-98-9

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. 3 ml of thionyl bromide is then added over 0.5 hour. The mixture is then stirred for a further 1 hour. 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 hydrobromide (3-a, R1=R2=H, R3=Et). 1H NMR (DMSO): 1.11 (6H), 1.61 (1H), 1.87 (1H), 2.73 (1H), 2.84 (1H), 3.04 (1H), 3.42 (1H), 4.01 (2H), 7.36 (3H), 7.47 (2H), 7.65 (4H), 8.03 (3H). 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-dcf1f83bca414f99b2b3d6211f47e53b
Source dataset
uspto-grants-2014_05
Patent number
US08716495B2

Reaction notes

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