4-Methylmorpholine → ethyl (S)-2-[3-(4-methoxyphenyl)propionylamino]-3-(4-nitrophenyl)propionate

HRID 1291014Notes

Reaction equation

HRID 1291014 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]([OH:13])=O)=[CH:5][CH:4]=1.Cl.[NH2:15][C@@H:16]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=1)[C:17]([O:19][CH2:20][CH3:21])=[O:18].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][C:11]([NH:15][C@@H:16]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([N+:29]([O-:31])=[O:30])=[CH:27][CH:28]=2)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[O:13])=[CH:7][CH:8]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 957503-(p-Methoxyphenyl)propionic acidHCID 6453710Ethyl 4-nitro-3-phenyl-L-alaninate monohydrochloride

Product 1

HCID 53690986ethyl (S)-2-[3-(4-methoxyphenyl)propionylamino]-3-(4-nitrophenyl)propionateYield 40.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Then, 3-(4-methoxyphenyl)propionic acid (330 mg, 1.83 mmol) and ethyl (S)-2-amino-3-(4-nitrophenyl)propionate hydrochloride (500 mg, 1.82 mmol) were dissolved in N,N-dimethylformamide (30 ml). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (384 mg, 2.00 mmol), 1-hydroxy-1H-benzotriazole (270 mg, 2.00 mmol) and N-methylmorpholine (0.25 ml, 2.27 mmol) were added, and the mixture was stirred at room temperature for 21 hours. Water (500 ml) was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. After filtration, low boiling matters were distilled away from the filtrate under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=2/1) to give 292 mg of ethyl (S)-2-[3-(4-methoxyphenyl)propionylamino]-3-(4-nitrophenyl)propionate as a colorless solid (40%). This solid (280 mg, 0.699 mmol) was dissolved in ethanol (30 ml) and 10% palladium-carbon (100 mg) was added. The mixture was refluxed under heating for 14 hours under a hydrogen atmosphere. The reaction mixture was cooled to room temperature and filtrated. Low boiling matters were distilled away from the filtrate under reduced pressure and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/1-3/7) to give 171 mg of ethyl (S)-3-(4-aminophenyl)-2-[3-(4-methoxyphenyl)propionylamino]propionate as a colorless solid (66%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationAfter filtration, low boiling matters
  5. distillationwere distilled away from the filtrate under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-479467a965b54078b9353b2399c886d7
Source dataset
uspto-grants-1998_05
Patent number
US05753670

Reaction notes

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