Thionyl Chloride → 5-Bromothiophene-2-carbonyl chloride

Participants

Reaction Conditions

Reaction Steps

Thionyl chloride (35 ml) is added dropwise to 5-bromo-2-thiophenecarboxylic acid (4.92 g, 23.77 mmol) at 0° C., and the mixture is then heated at 90° C. overnight. After the mixture has cooled to room temperature, the solvent is removed in vacuo, and the residue is washed with cold heptane. 5-Bromothiophene-2-carbonyl chloride is obtained as an almost white solid. 3,5-Difluorobenzylamine (209 mg, 1.46 mmol) is added to a mixture of 5-bromothiophene-2-carbonyl chloride (300 mg, 1.33 mmol), piperidinomethylpolystyrene (410 mg, 3.5 mmol/g, 1.44 mmol) in anhydrous dichloromethane (5 mL) and stirred for 2.5 hr. The reaction mixture is diluted with dichloromethane and filtered through silica gel. The filtrate is concentrated to afford 5-bromo-thiophene-2-carboxylic acid 3,5-difluoro-benzylamide as a white solid (400 mg, 90% yield).

Provenance & Evidence