Phosphorus tribromide → HCID 15735716, compound

Participants

Reaction Steps

Phosphorus tribromide (4.2 mL, 1 M solution in dichloromethane) is added dropwise to a solution of 2-[[3-(1-hydroxyethyl)-2-methylphenyl]amino]benzoic acid methyl ester (2.0 g, 7.0 mmol) and pyridine (2 drops) in dicholoromethane (50 mL) at 0° C. After the reaction mixture is stirred at room temperature for 1 hour, it is poured into a solution of O-tetrahydropyranylhydroxylamine (8.2 g, 70 mmol) in dimethylformamide (50 mL). The dichloromethane is evaporated under reduced pressure, and the reaction mixture is stirred overnight at room temperature. The reaction mixture is diluted with 200 mL water and extracted with 300 mL ether. The organic layer is washed with water and brine, and then evaporated to an oil. The crude intermediate THP-protected hydroxylamine is taken up in methanol and acidified with concentrated HCl to pH=1. The reaction mixture is heated at reflux for 30 minutes, cooled, and quenched by the careful addition of saturated aqueous sodium bicarbonate. The methanol is evaporated under reduced pressure and the product is extracted into ethyl acetate. The organic layer is washed with brine, dried over magnesium sulfate, and evaporated to give the crude hydroxylamine as an oil.

Provenance & Evidence