Hydrochloric Acid → 5-Chloro-2-fluoro-4-((1-(trifluoromethyl)-cyclopentyl)methoxy)benzoic acid

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Reaction Steps

To a solution of (1-(trifluoromethyl)cyclopentyl)methanol (2.80 g, 16.65 mmol) in anhydrous dimethylsulfoxide (50 ml) was added potassium tert-butoxide (4.50 g, 40.106 mmol) and the reaction mixture was stirred at ambient temperature for 30 minutes. 5-chloro-2,4-difluorobenzoic acid (3.20 g, 16.62 mmol) was added to the reaction mixture, and stirring was continued for 2 hours. The reaction mixture was acidified to pH=1 with 5% aqueous hydrochloric acid solution and extracted with ethyl acetate, the combined organic extracts was washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (30% ethyl acetate in hexanes) afforded the title compound (5.00 g, 88%) containing o-substituted regioisomer, which was used for next step without further purification: MS (ES−) m/z 339.2, 341.2 (M−1).

Provenance & Evidence