Under argon protection, 4-(1-hydroxy-1-trifluoromethyl-2,2,2-trifluoroethyl)aniline (A) (1.5 M THF solution, 128 μL, 0.193 mmol) was dissolved in acetone (643 μL). Subsequently, 2,6-dimethylpyridine (29 μL, 0.251 mmol) and 2-thiophenesulfonyl chloride (0.193 mmol) were added sequentially and the reaction was carried out at room temperature. The reaction mixture was heated to 80 °C for 1 day. After completion of the reaction, it was cooled to room temperature and diluted with ethyl acetate (EtOAc) and saturated sodium bicarbonate (NaHCO3) solution. The aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated. The crude product was purified by silica gel column chromatography using hexane/ethyl acetate (7/3) as eluent to afford the target product N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-2-thiophene-sulfonamide (SR3335) as a white powder in 48 mg (62% yield). The compound has a CAS number of 2937-53-05-6 and is known in the literature and commercially available.
