Thionyl Chloride → 5-[3-(1,1-dimethylethyl)-1H-pyrazol-1-yl]-3-[3-(trifluoromethyl)phenyl]-4-thiazolidinone

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of thionyl chloride (5.3 mL, 73 mmol) in 120 mL of methylene chloride at ˜10° C. was slowly added 3-(1,1-dimethylethyl)-1H-pyrazole (11.32 g, 91 mmol). The resulting solution was stirred for ˜20 minutes and was then cooled further to ˜0° C. To this solution was added N,N-diisopropylethylamine (26.5 mL, 152 mmol) dropwise at ˜0° C. and then 5-hydroxy-3-[3-(trifluoromethyl)phenyl]4thiazolidinone (16 g, 61 mmol) portionwise at temperatures between 0° C. and 10° C. After the addition, the reaction mixture was allowed to warm up to room temperature, and stirred at room temperature for 3 days. To the reaction mixture was then added 120 mL of concentrated sodium bicarbonate aqueous solution. The methylene chloride layer was separated and the aqueous layer was extracted twice with methylene chloride (˜120 mL each). The methylene chloride layers were combined, dried over MgSO4 and then concentrated. The residue was loaded on silica gel in a flash chromatography column and eluted with hexanes followed by methylene chloride to give 15.74 g of a crude product. The crude product was further purified by trituration in hexanes followed by filtration to give the title compound, a compound of this invention, as a tan solid (11.8 g) melting at 66–69° C.

Provenance & Evidence