4-Phenylbutyric Acid → N-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(4-phenylbutyryl)-L-asparaginyl]amino]butyl]-L-proline tert.butyl ester

HRID 742847

Reaction equation

HRID 742847 reaction equation
[C:1]([O:5][C:6](=[O:32])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[CH2:12][C@@H:13]([OH:31])[C@@H:14]([NH:22][C:23](=[O:30])[C@H:24]([CH2:26][C:27](=[O:29])[NH2:28])[NH2:25])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([CH3:4])([CH3:3])[CH3:2].[C:33]1([CH2:39][CH2:40][CH2:41][C:42](O)=[O:43])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.OC1C2N=NNC=2C=CC=1.C(N1CCOCC1)C.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:32])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[CH2:12][C@@H:13]([OH:31])[C@@H:14]([NH:22][C:23](=[O:30])[C@H:24]([CH2:26][C:27](=[O:29])[NH2:28])[NH:25][C:42](=[O:43])[CH2:41][CH2:40][CH2:39][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 47754-Phenylbutyric AcidHCID 7525EthylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 70041604N-[3(S)-[[L-asparaginyl]amino]-2(R)-hydroxy-4-phenylbutyl]-L-proline tert.butyl esterHCID 178418300HCID 178418300, compound

Product 1

HCID 70043657N-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(4-phenylbutyryl)-L-asparaginyl]amino]butyl]-L-proline tert.butyl esterYield 22.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 270 mg of N-[3(S)-[[L-asparaginyl]amino]-2(R)-hydroxy-4-phenylbutyl]-L-proline tert.butyl ester and 98 mg of 4-phenylbutyric acid in 10 ml of dry tetrahydrofuran was cooled in an ice/salt mixture. 81 mg of hydroxybenzotriazole, 69 mg of N-ethylmorpholine and 136 mg of dicyclohexylcarbodiimide were added and the mixture was stirred for 64 hours. The mixture was then diluted with ethyl acetate and filtered. The filtrate was washed with aqueous sodium bicarbonate solution and sodium chloride solution. The solvent was removed by evaporation and the residue was chromatographed on silica gel using System G for the elution to give 79 mg of N-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(4-phenylbutyryl)-L-asparaginyl]amino]butyl]-L-proline tert.butyl ester as a white solid; MS: m/e 595 [M+H]+.

Workup

  1. filtrationfiltered
  2. washThe filtrate was washed with aqueous sodium bicarbonate solution and sodium chloride solution
  3. customThe solvent was removed by evaporation
  4. customthe residue was chromatographed on silica gel using System G for the elution

Sources & evidence

ORD record
ord-6a5d8f30925641e8b669ced145b435bc
Source dataset
uspto-grants-1996_09
Patent number
US05554756

Linked notes

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