Ammonium Chloride → Tert-butyl (5-chloro-2,4-difluorophenyl)sulfonyl(thiazol-4-yl)carbamate

Participants

Reaction Steps

To a solution of thiazol-4-yl-carbamic acid tert-butyl ester (Preparation 3, 503 mg, 2.51 mmol) in tetrahydrofuran (5.0 mL) cooled to −78° C. was added lithium hexamethyldisilazide (1.0 M in tetrahydrofuran, 2.76 mL, 2.76 mmol). The reaction mixture was stirred for 30 minutes at ambient temperature then cooled to −78° C. A solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride (620.5 mg, 2.51 mmol) in tetrahydrofuran (5.0 mL) was added slowly via a syringe. After the addition was complete, the reaction mixture was allowed to warm gradually to ambient temperature. After 24 hours, the reaction mixture was poured into saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo onto diatomaceous earth. The residue was purified by automated silica gel flash chromatography (0% to 5% ethyl acetate in dichloromethane gradient elution) to afford the title compound as a white solid (733 mg).

Provenance & Evidence