N-(2-chloro-4-nitrobenzoyl)-4-(2-methoxyphenyl)-L-phenylalanine methyl ester → N-(4-amino-2-chlorobenzoyl)-4-(2-methoxyphenyl)-L-phenylalanine methyl ester

HRID 24652Notes

Reaction equation

HRID 24652 reaction equation
[CH3:1][O:2][C:3](=[O:33])[C@H:4]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:31][CH3:32])=[CH:21][CH:20]=1)[NH:5][C:6](=[O:17])[C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][C:8]=1[Cl:16]>CO.[Ni]>[CH3:1][O:2][C:3](=[O:33])[C@H:4]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:31][CH3:32])=[CH:21][CH:20]=1)[NH:5][C:6](=[O:17])[C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][C:8]=1[Cl:16]

Participants

4

Reactant 1

HCID 53828542N-(2-chloro-4-nitrobenzoyl)-4-(2-methoxyphenyl)-L-phenylalanine methyl ester

Product 1

HCID 54392214N-(4-amino-2-chlorobenzoyl)-4-(2-methoxyphenyl)-L-phenylalanine methyl esterYield 91.1%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

Ra—Ni (0.4 mL of 50% dispersion in water) was added to a solution of N-(2-chloro-4-nitrobenzoyl)-4-(2-methoxyphenyl)-L-phenylalanine methyl ester (1.04 g) in anhydrous MeOH (50 mL) and the mixture was stirred at room temperature under H2 atmosphere for 3.5 h. The mixture was then filtered over Celite and washed with MeOH. The filtrate was evaporated and the residue was purified by flash column chromatography (silica gel; eluent: CH2Cl2/MeOH 100:1 to 20:1) to give N-(4-amino-2-chlorobenzoyl)-4-(2-methoxyphenyl)-L-phenylalanine methyl ester (887 mg). ESMS: m/z 439 (MH+). The product obtained above was also prepared via the coupling of 4-(2-methoxyphenyl)-L-phenylalanine methyl ester hydrochloride with 4-amino-2-chlorobenzoic acid using EDC and HOBT in an analogous manner as described in Example 2.

Workup

  1. filtrationThe mixture was then filtered over Celite
  2. washwashed with MeOH
  3. customThe filtrate was evaporated
  4. customthe residue was purified by flash column chromatography (silica gel; eluent: CH2Cl2/MeOH 100:1 to 20:1)

Sources & evidence

ORD record
ord-700fceac696242b5b9b5763ebd42cf0b
Source dataset
uspto-grants-2005_02
Patent number
US06855843B2

Reaction notes

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