Triethylamine → 2',4'-Difluoro-2-methanesulfonyloxypropiophenone

Participants

Reaction Steps

2',4'-Difluoro-2-hydroxypropiophenone (2.8 g) was dissolved in methylene chloride (28 ml), to which were added triethylamine (2.5 ml) and methanesulfonyl chloride (1.3 ml) at 0° C. After stirring for 15 minutes, the mixture was washed with water (30 ml), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (3 cm×10 cm) and eluted with methylene chloride. The desired fraction was concentrated, to give 2',4'-difluoro-2-methanesulfonyloxypropiophenone (3.0 g) as a colorless oil. This compound (3.0 g) was dissolved in 30 ml of N,N-dimethylformamide, to which were added 1H-1,2,4-triazole (0.94 g) and then 60% sodium hydride suspension in oil (0.5 g) at -10° C. After stirring at 0° C. for 50 minutes, the reaction mixture was added to a mixture of ethyl acetate (100 ml) and water (200 ml) for extraction. The water layer was extracted with ethyl acetate (100 ml) and the ethyl acetate layers were combined, washed with saturated aqueous solution of sodium chloride (30 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (3 cm×10 cm) and eluted with ethyl acetate. The desired fraction was concentrated, to give 2',4'-difluoro-2-(1H-1,2,4-triazol-1-yl)propiophenone (1.5 g) as a colorless oil. This compound (1.24 g) was added to a mixture of dimethyl sulfoxide (30 ml), 60% sodium hydride suspension in oil (0.25 g) and trimethylsulfoxonium iodide (1.38 g) at 10° C. and then the temperature was raised to 25° C. Two hours later, the reaction mixture was added to a mixture of diethyl ether (100 ml) and water (150 ml), diethyl ether layer was separated, and the water layer was extracted with diethyl ether (100 ml×2). The organic layers were combined, washed with saturated aqueous solution of sodium chloride (50 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (3 cm×10 cm) and eluted with ethyl acetate-hexane (3:1), to give 2-(2,4-difluorophenyl)-2-[1-(1H-1,2,4-triazol-1-yl)ethyl]oxirane as a colorless oil (0.87 g).

Provenance & Evidence