Hydrochloric Acid → Ethyl 4-(chlorosulfonyl)-3-fluorobenzoate

Participants

Reaction Conditions

Reaction Steps

4-amino-3-fluoro-benzoic acid ethyl ester (490 mg, 2.7 mmol) was dissolved in acetonitrile (20 mL, 400 mmol) at ambient temperature. The solution was cooled to −5° C. in an acetone bath. 37% HCl (37:63, HCl:water, 2 mL) was added slowly. A solution of sodium nitrite (203 mg, 2.94 mmol) in water (1 mL, 60 mmol) was added slowly. The reaction mixture turned orange over the course of the addition. After addition was complete, the reaction mixture was stirred at 0° C. for 35 min. A 0° C. solution of sulfur dioxide in AcOH (8:25, sulfur dioxide:AcOH, 20 mL) was added followed by copper(II) chloride dihydrate (460 mg, 2.7 mmol). No gas evolution was evident. The mixture warmed to ambient temperature and stirred for 1.5 hours. The reaction mixture was poured into 20 mL of water and extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The concentrate contained a large excess of AcOH. The residue was diluted with acetonitrile and water, frozen, and lyophilized to afford a mauve powder (559 mg, 74%).

Provenance & Evidence