L-Alanyl-L-proline → Enalaprilat Benzyl Ester

HRID 1758854Notes

Reaction equation

HRID 1758854 reaction equation
[NH2:1][C@H:2]([C:4]([N:6]1[CH2:13][CH2:12][CH2:11][C@H:7]1[C:8]([OH:10])=[O:9])=[O:5])[CH3:3].O=[C:15]([CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17].C([BH3-])#N.[Na+]>C(O)C>[CH2:19]([O:18][C:16]([C@@H:15]([NH:1][C@H:2]([C:4]([N:6]1[CH2:13][CH2:12][CH2:11][C@H:7]1[C:8]([OH:10])=[O:9])=[O:5])[CH3:3])[CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:17])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 83525L-Alanyl-L-prolineHCID 5003444Sodium cyanoborohydrideHCID 18370473Benzyl 2-oxo-4-phenylbutanoate

Product 1

HCID 22822716Enalaprilat Benzyl Ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of L-alanyl-L-proline (167 mg) and benzyl 2-oxo-4-phenylbutyrate (1.20 g) in 5 ml of ethanol is stirred at room temperature with 3 g of powdered molecular sieves, type 4A. Sodium cyanoborohydride (75 mg) is then added in portions over the course of three hours. The product is purified by absorption on strong cation exchange resin and elution with 2% pyridine in water. After passage through a gel filtration (LH-20) column 220 mg of N-(1-benzyloxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline is obtained as a mixture of isomers. Thin layer chromatography on silica gel eluted with 1 EtOAc, 1 n-butanol, 1 H2O, 1 HOAc shows one main post, Rf 0.71. Isomers are separated using reverse phase HPLC to yield N-(1(S)-benzyloxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline.

Workup

  1. customThe product is purified by absorption on strong cation exchange resin and elution with 2% pyridine in water
  2. filtrationAfter passage through a gel filtration (LH-20) column 220 mg of N-(1-benzyloxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline
  3. customis obtained as a mixture of isomers
  4. washThin layer chromatography on silica gel eluted with 1 EtOAc, 1 n-butanol, 1 H2O, 1 HOAc
  5. customIsomers are separated

Sources & evidence

ORD record
ord-d0de89bb7d8f491f8e70d67f4aba2352
Source dataset
uspto-grants-1983_02
Patent number
US04374829

Reaction notes

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