Dichloromethane → 5-(3,3-Difluoropyrrolidine-1-carbonyl)-N-methyl-N-propyl-isophthalamic acid ethyl ester

Participants

Reaction Steps

Dissolve 5-(methyl-propylcarbamoyl)-isophthalic acid monoethyl ester (667 mg, 2.3 mmol) in a 0.1 N 1-hydroxybenzotriazole solution of 1:1:5 tert-butanol:acetonitrile:dichloromethane (23 mL, 2.3 mmol). Stir the solution at room temperature for 5 min, add 3,3-difluoropyrrolidine hydrochloride (331 mg, 2.3 mmol) and triethylamine (640 μL, 4.6 mmol). Stir the reaction at room temperature for 2 h, add ethyl acetate (100 mL) and wash with saturated aqueous ammonium chloride (2×30 mL), saturated aqueous sodium chloride (30 mL), dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 50:50 ethyl acetate:hexanes) to give the title compound (270 mg, 31%).

Provenance & Evidence