Diphosgene → HCID 178450552, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of diphosgene (29 μL, 0.24 mmol) in 1:1 v/v toluene/tetrahydrofuran (20 mL) at −78° C. under an atmosphere of nitrogen was added a solution of (R)-2-amino-2-[4-(2-tert-butoxy-ethoxy)-phenyl]-N-[(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-phenyl-ethyl]-acetamide (210 mg, 0.34 mmol) and N,N-diisopropylethylamine (239 μL, 1.37 mmol) in tetrahydrofuran (6 mL) dropwise with stirring. The reaction was allowed to warm to −20° C. then quenched with ice water (10 mL) and stirred for 10 minutes. The mixture was poured into ethyl acetate (30 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (20 mL) and the organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted with 20 to 60% v/v ethyl acetate/hexanes to give (R)-5-[4-(2-tert-butoxy-ethoxy)-phenyl]-3-[(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-phenyl-ethyl]-imidazolidine-2,4-dione (140 mg, 64%).

Provenance & Evidence