Ethanol → Sacubitril N-Boc Ester

HRID 1477452Notes

Reaction equation

HRID 1477452 reaction equation
[CH2:1]([O:3][C:4](=[O:30])[C:5](=[CH2:29])[CH2:6][C@H:7]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH3:2].C(O)C.[H][H]>[Pd].C(N(CC)CC)C>[CH2:1]([O:3][C:4](=[O:30])[CH:5]([CH3:29])[CH2:6][CH:7]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[CH3:2]

Participants

6

Reactant 3

HCID 702EthanolHCID 66958146(R)-5-Biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentanoic acid ethyl ester2×HCID 178418361HCID 178418361, compound

Product 1

HCID 58160380Sacubitril N-Boc Ester

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8471TriethylamineSolvent

Procedure

500 mg (R)-5-Biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylenepentanoic acid ethyl ester (2-a, R1=Boc, R2=H, R3=CO2Et) is added to ethanol (5 ml) at ambient temperature. Triethylamine (170 μl) is then added to the mixture. 50 mg Palladium on carbon (10%, 50% water-wet, Degussa E101 NE/W) is then added. Hydrogen gas at ambient pressure is applied to the mixture. The mixture is then stirred overnight at ambient temperature and pressure. The mixture is then filtered and concentrated under reduced pressure to afford 2R,4S)-5-Biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid ethyl ester (1-a, R1=Boc, R2=H, R3=CO2Et) and (2S,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid ethyl ester (1-b, R1=Boc, R2=H, R3=CO2Et). Spectroscopic data as in Example 63. Ratio of diastereomers 70:30 (1-a, R1=Boc, R2=H, R3=CO2Et:1-b, R1=Boc, R2=H, R3=CO2Et) as determined by hplc (hplc method as in Example 65)

Workup

  1. filtrationThe mixture is then filtered
  2. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-012cc5e88d8f4d6faf3c5614adbbcbd3
Source dataset
uspto-grants-2016_08
Patent number
US09403766B2

Reaction notes

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