Diphosgene → HCID 16722197, compound

Participants

Reaction Steps

To a solution of diphosgene (20 μL, 0.17 mmol) in 1:1 v/v toluene/tetrahydrofuran (16 mL total) at −35° C. under an atmosphere of dry argon was added a solution of (2S,3S)-2-[(R)-2-amino-2-(4-methoxy-phenyl)-acetylamino]-N-(4-bromo-phenyl)-3-phenyl-butyramide (120 mg, 0.24 mmol) and N,N-diisopropylethylamine (210 μL, 1.2 mmol) in tetrahydrofuran (8 mL) dropwise with stirring over 10 minutes. After an additional 45 minutes ice was added and the reaction mixture stirred vigorously and warmed to ambient temperature. The reaction mixture was poured into water, extracted with ethyl acetate (twice) and the combined organic layers were washed sequentially with water (twice), 0.1 M aqueous hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate, water and brine, then dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel eluted with 2:1 v/v hexanes/ethyl acetate. The isolated product was dissolved in a small volume of dichloromethane and then precipitated by dropwise addition to a vigorously stirred large volume of petroleum ether. The precipitated solid was isolated by filtration and dried in vacuo to give (2S,3S)—N-(4-bromo-phenyl)-2-[(R)-4-(4-methoxy-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-butyramide as a colorless solid (87 mg, 69%).

Provenance & Evidence