Ammonium Chloride → 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

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Reaction Steps

To a solution of N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (Preparation 5, 899 mg, 3.58 mmol) in tetrahydrofuran (6.0 mL) cooled to −78° C., was added lithium hexamethyldisilazide (1.0 M in tetrahydrofuran, 4.3 mL) dropwise. The reaction mixture was stirred for 35 minutes at ambient temperature, then cooled again to −78° C. before the dropwise addition of 5-chloro-2,4-difluorobenzenesulfonyl chloride (850 mg, 3.4 mmol). The reaction mixture was stirred at −78° C. for 1 hour then at ambient temperature for 4 hours. The reaction mixture was poured into saturated aqueous ammonium chloride solution and extracted with dichloromethane. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by automated silica gel flash chromatography (0% to 10% ethyl acetate in hexanes gradient elution) to afford the title compound as a white solid (1.16 g, 73%).

Provenance & Evidence