2,3,3-Trifluoro-1-hydroxy-4-n-propylbicyclo[2.2.2]octane (4) (37.5 mg), and 4-bromomethyl-1-ethoxy-2,3-difluorobenzene (5) (65.4 mg) were added to a dimethyl formamide suspension (2.0 mL) of sodium hydride (4.9 mg), the mixture was stirred at room temperature for 2.5 hours, and then added with saturated aqueous ammonium chloride solution to thereby terminate the reaction. The organic layer was extracted three times with ethyl acetate, the organic layers were combined, and washed with saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, and the solvent was then vaporized off under reduced pressure, to thereby obtain a crude product. The crude product was purified by silica gel column chromatography (hexane/ethyl acetate=9:1), to thereby obtain 1-(4′-ethoxy-2′,3′-difluorophenyl)methyloxy-2,3,3-trifluoro-4-n-propyl bicyclo[2.2.2]octane (6) (yield=39.9 mg, yield ratio=60%) as a colorless clear crystal.
