Triethylamine → (2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl methanesulfonate

Participants

Reaction Steps

In a mixture of ethyl acetate (40 ml) and dichloromethane (10 ml) was dissolved (2R,3R)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol (1.25 g). To the solution were added, under ice-cooling, triethylamine (0.84 ml) and methanesulfonyl chloride (0.48 ml), which was stirred for 30 minutes at room temperature. To the reaction mixture was added ethyl acetate (50 ml), which was washed with water, dried (anhydrous magnesium sulfate) and concentrated to give (2R,3R)-2-(2,4-difluorophenyl)-3-methanesulfonyloxy-1-(1H-1,2,4-triazol-1-yl)-2-butanol as an oily product. The product was dissolved in methanol (40 ml), to which was added a 28% methanol solution of sodium methylate (1.16 ml) under ice-cooling. The mixture was stirred for 30 minutes at room temperature. The reaction mixture was concentrated under reduced pressure to a volume of about 10 ml. To the concentrate was added ethyl acetate (100 ml), and the mixture was washed with water, then dried (anhydrous magnesium sulfate), followed by distilling off the solvent under reduced pressure. The residue was purified by means of a silica gel chromatography (eluent: ethyl acetate-dichloromethane=4:1), which was then recrystallized from a mixture of ethyl acetate and hexane to afford (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane (520 mg) as colorless needles. m.p. 89°-90° C. [α]D23 =-8.3° (c=1.0 in MeOH)

Provenance & Evidence