Tetrahydrofuran → 3-(N-(4-Chloro-3-methylisoxazol-5-yl)sulfamoyl)thiophene-2-carboxylic acid

Participants

Reaction Steps

To a mixture of sodium hydride (60%, 2.1 g, 52 mmol) and tetrahydrofuran (20 mL) was added a mixture of 4-chloro-3-methyl-1,2-oxazol-5-amine (3.0 g, 23 mmol) and tetrahydrofuran (20 mL) at 0° C., followed by stirring at that temperature for 30 minutes. Methyl 3-(chlorosulfonyl)thiophene-2-carboxylate (5.3 g, 22 mmol) was added at that temperature to the reaction mixture, which was then stirred for 1 hour at 0° C., and then stirred for 4 hours at room temperature. Hexane (100 ml) was added at room temperature to the reaction mixture, and the precipitated solid was collected by filtration. Methanol (20 mL) was added to the solid, followed by a 2N aqueous solution of sodium hydroxide (20 mL), and the reaction mixture was stirred for 5 hours at room temperature. The solvent was distilled away under reduced pressure, and ice water (20 mL) was added to the residue, followed by a 2 N aqueous solution of hydrochloric acid (20 mL). The precipitated solid was collected by filtration to give the title compound (2.5 g, 35% yield).

Provenance & Evidence