Pyridine → [(5-Chloro-benzo[b]thiophen-3-yl)-[2-(3,4-difluoro-phenyl)-vinylcarbamoyl]-methyl}-methyl-phosphinic acid

Participants

Reaction Conditions

Reaction Steps

A 1 L four-necked round-bottomed flask equipped with mechanical stirrer, addition funnel, condenser, and a thermocouple was charged with {(5-Chloro-benzo[b]thiophen-3-yl)-[2-(3,4-difluoro-phenyl)-vinylcarbamoyl]-methyl}-methyl-phosphinic acid ethyl ester (26.4 g, 0.056 mol), acetonitrile (200 mL) and pyridine (11.0 mL, 0.136 mol). To the resulting mixture was then added bromotrimethylsilane (15.5 mL, 0.117 mol), 15 minutes, while maintaining the temperature of the resulting mixture below about 30° C. The mixture was then stirred for an additional 15 minutes to yield a clear yellow solution, which was aged for about 2 hours. The resulting mixture was then cooled to about 0-5° C. To the mixture was then added concentrated sulfuric acid (5.4 mL) in water (90 mL), using vigorous agitation. To the resulting mixture was then added MTBE (150 mL) and the mixture aged with stirring until two homogeneous layers were obtained. The layers were separated and the organic layer was washed twice with water (45 mL) and then concentrated to yield a residue. The residue was digested with methanol (180 mL) under vigorous stirring. then concentrated to about 50% of its original volume under reduced pressure. The resulting slurry was cooled to about 0-5° C., then aged at this temperature for about 1 hours. The resulting solids were filtered, washed twice with cold methanol (18 mL), dried in a vacuum oven at 50° C., overnight, to yield the title compound as a white crystalline solid

Provenance & Evidence