4-Nitrophenol → Z-Phe-ONp

HRID 1590116Notes

Reaction equation

HRID 1590116 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:20]([OH:22])=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:23]1[C:28]([N+:29]([O-:31])=[O:30])=[CH:27][CH:26]=[C:25](O)[CH:24]=1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[N+:29]([C:28]1[CH:23]=[CH:24][C:25]([O:21][C:20](=[O:22])[C@H:12]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[NH:11][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])=[CH:26][CH:27]=1)([O-:31])=[O:30]

Participants

5

Reactant 3

HCID 9804-NitrophenolHCID 10868DicyclohexylcarbodiimideHCID 70878Benzyloxycarbonyl-L-phenylalanine

Product 1

HCID 151025Z-Phe-ONp

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-Benzyloxycarbonyl-L-phenylalanine (2.99 g) and p-nitrophenol (1.39 g) are dissolved in tetrahydrofuran (30 ml), and dicyclohexylcarbodiimide (2.1 g) is added thereto under ice-cooling. The mixture is stirred at room temperature for four hours and insoluble materials are filtered off. Ethyl acetate is added to the filtrate and the mixture is washed with an aqueous sodium bicarbonate solution and an aqueous sodium chloride solution, dried, and then concentrated to remove solvent. Hexane is added to the residue to give N-benzyloxycarbonyl-L-phenylalanine-p-nitrophenyl ester as crystals. The product is dissolved in tetrahydrofuran (20 ml), and a solution(15 ml) of L-histidine methyl ester dihydrochloride (2.4 g) and triethylamine (2.8 ml) in water is added thereto under ice-cooling, and the mixture is stirred at room temperature overnight. The reaction mixture is concentrated under reduced pressure to remove solvent. The residue is purified by silica gel column chromatography (solvent; chloroform:methanol=15:1) and crystallized with ethyl acetate to give N-benzyloxycarbonyl-L-phenylalanyl-L-histidine methyl ester (2.8 g) as colorless crystals. Yield ; 64.1%

Workup

  1. temperatureunder ice-cooling
  2. filtrationinsoluble materials are filtered off
  3. additionEthyl acetate is added to the filtrate
  4. washthe mixture is washed with an aqueous sodium bicarbonate solution
  5. dry with materialan aqueous sodium chloride solution, dried
  6. concentrationconcentrated
  7. customto remove solvent
  8. additionHexane is added to the residue

Sources & evidence

ORD record
ord-10e394695b0b43e3bfeecdeb5bb5350b
Source dataset
uspto-grants-1993_04
Patent number
US05202312

Reaction notes

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