4-Nitroaniline → N-(4-Nitrophenyl)glycine ethyl ester

Participants

Reaction Steps

4-Nitroaniline (25.0 g, 181 mmol) and ethyl bromoacetate (10.0 ml, 90.5 mmol) were stirred at 80°-90° C. for 20 hours under a nitrogen atmosphere. Ethyl acetate (30 ml) was added to the reaction mixture and the mixture was refluxed under heating for 10 minutes. The obtained solid was collected by filtration and recrystallized from ethanol to give 13.1 g of ethyl (4-nitroanilino)acetate as a yellow solid (64%). This solid (1.00 g, 4.46 mmol) and benzyloxycarbonyl chloride (8 ml) were stirred at 80°-90° C. for 1.5 hours under a nitrogen atmosphere. Toluene (20 ml) was added to the reaction mixture and low boiling matters were distilled away under reduced pressure, which was followed by purification by silica gel column chromatography (n-hexane/ethyl acetate=5/2) to quantitatively give 962 mg of ethyl [4-nitro-N-(benzyloxycarbonyl)anilino]acetate as a yellow oil. Ethanol (100 ml) and water (30 ml) were added to the oil (716 mg, 2.00 mmol) and activated zinc (6.55 g, 100 mmol) and calcium chloride (2.22 g, 20.0 mmol) were added, which was followed by refluxing under heating for 2 hours. The reaction mixture was filtrated and low boiling matters were distilled away from the filtrate under reduced pressure. Water (100 ml) was added to the residue and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After filtration, low boiling matters were distilled away from the filtrate under reduced pressure to give 576 mg of ethyl [4-amino-N-(benzyloxycarbonyl)anilino]acetate as a yellow oil (88%).

Provenance & Evidence