Hydrochloric Acid → ethyl (S)-2-(benzyloxycarbonylamino)-3-(4-nitrophenyl)propionate

HRID 1682673Notes

Reaction equation

HRID 1682673 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[OH-].[Na+].[CH2:21]([O:28][C:29](Cl)=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])O.[Na+]>O1CCCC1.O>[CH2:21]([O:28][C:29]([NH:2][C@@H:3]([CH2:9][C:10]1[CH:11]=[CH:12][C:13]([N+:16]([O-:18])=[O:17])=[CH:14][CH:15]=1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10387Benzyl chloroformateHCID 14798Sodium Hydroxide2×HCID 516892Sodium BicarbonateHCID 6453711Ethyl 4-nitro-L-phenylalanine

Product 1

HCID 14036702ethyl (S)-2-(benzyloxycarbonylamino)-3-(4-nitrophenyl)propionateYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Hydrochloride (1.00 g, 3.64 mmol) of ethyl (S)-2-amino-3-(4-nitrophenyl)propionate was dissolved in a mixed solution of tetrahydrofuran (10 ml), water (10 ml) and a 1N aqueous sodium hydroxide solution (3.64 ml) and a solution of benzyloxycarbonyl chloride (0.57 ml, 3.99 mmol) dissolved in tetrahydrofuran (3.5 ml) and a 1N aqueous sodium hydroxide solution (3.64 ml, 3.64 mmol) were simultaneously added dropwise under ice-cooling, which was followed by stirring at room temperature for 4 hours. A saturated aqueous sodium hydrogen carbonate solution (30 ml) was added, 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=1/1) to give 743 mg of ethyl (S)-2-(benzyloxycarbonylamino)-3-(4-nitrophenyl)propionate as a colorless solid (55%). This solid (724 mg, 1.94 mmol) was dissolved in a mixture of ethanol (120 ml) and water (30 ml), and zinc (6.40 g, 97.9 mmol) and calcium chloride (2.00 g, 18.0 mmol) were added. The mixture was refluxed under heating for 3.5 hours. The reaction mixture was cooled to room temperature and filtrated. The filtrate was concentrated and water (100 ml) was added to the filtrate. The mixture was extracted with ethyl acetate, and 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 to give 572 mg of ethyl (S)-3-(4-aminophenyl)-2-(benzyloxycarbonylamino)propionate as a pale-yellow oil (86%).

Workup

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

Sources & evidence

ORD record
ord-4d213087f6f64fddb659f4722dd0b129
Source dataset
uspto-grants-1997_06
Patent number
US05635527

Reaction notes

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