4-Chloro-3-sulfamoylbenzoic acid → 3-(Aminosulfonyl)-4-chlorobenzoyl chloride

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Reaction Steps

4-Chloro-3-sulfamoyl-benzoic acid (5 g) is treated with 20.5 mL of thionyl chloride and heated to reflux for 5.5 h. Thionyl chloride is removed and the residue is dried at 50° C. in vacuo to give 5.6 g of 4-chloro-3-sulfamoyl-benzoyl chloride as a tan powder. This material is taken up in 28 mL of methylene chloride and treated at 0° C. with 2.64 g of N,O-dimethylhydroxylamine hydrochloride followed by 10.9 mL of pyridine and stirred overnight at room temperature. The reaction mixture is quenched at 0° C. with 19 mL of 3 N aqueous HCl and extracted with ethyl acetate. The organics are combined, washed with saturated aqueous sodium bicarbonate, 0.1 N aqueous HCl and a saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. The resulting crystals are filtered through a short pad of silica gel (1:2 hexanes/ethyl acetate) to give the title compound as a white powder. MS (m/z): (M−1) 277; Rf 0.36 (1:2 hexanes/ethyl acetate).

Provenance & Evidence