Chlorosulfonic acid → 5-[2-(Acetylamino)-4-methyl-1,3-thiazol-5-yl]thiophene-2-sulfonyl chloride

Participants

Reaction Conditions

Reaction Steps

N-[4-methyl-5-(2-thienyl)-1,3-thiazol-2-yl]acetamide, prepared in Step I (500 mg; 2.10 mmol; 1 eq.) is dissolved in DCM (30 ml). The reaction mixture is cooled down to 0° C. and chlorosulfonic acid (0.70 ml; 10.49 mmol; 5 eq.) dissolved in DCM (30 ml) is added dropwise over 15 min. The solution becomes pink. It is stirred 15 minutes at 0° C. Phosphorus pentachloride (873.7 mg; 4.20 mmol; 2 eq.) and phosphorus oxide chloride (0.78 ml; 8.39 mmol; 4 eq.) are added successively. The reaction mixture is stirred for 2 additional hours at room temperature. It is poured on ice and the desired product is extracted with 2 portions of EtOAc, dried over MgSO4, and evaporated, affording 5-[2-(acetylamino)-4-methyl-1,3-thiazol-5-yl]thiophene-2-sulfonyl chloride as yellow solid (650 mg; 92%). M− (ESI): 335.08; M+ (ESI): 337.08.

Provenance & Evidence