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

(2R,3R)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol (1.25 g) was dissolved in a mixture of ethyl acetate (40 ml) and dichloromethane (10 ml), to which triethylamine (0.84 ml) and methanesulfonyl chloride (0.48 ml) were added under ice-cooling. The resultant solution was stirred for 30 minutes at room temperature. After adding ethyl acetate, the reaction mixture was washed with water, dried over anhydrous magnesium sulfate and concentrated to obtain (2R,3R)-2-(2,4-difluorophenyl)-3-methanesulfonyloxy-1-(1H-1,2,4-triazol-1-yl)-2-butanol as an oil. Thus obtained compound was dissolved in methanol (40 ml), to which sodium methylate methanolic solution (1.16 ml, 28%) was added under ice-cooling. The resultant solution was stirred for 30 minutes at room temperature. The reaction mixture was concentrated to about 10 ml under reduced pressure, and the residue was extracted with ethyl acetate (100 ml). The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate and distilled off the solvent under reduced pressure. The residue was subjected to a silica gel column chromatography (ethyl acetate- dichloromethane=4:l) for purification and then recrystallized from a mixture of ethyl acetate and hexane to give (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane (520 mg) as colorless needles.

1. additionwere added under ice-
2. temperaturecooling
3. washthe reaction mixture was washed with water
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated

ORD record

ord-8442e9e3e5574ef3931c57d1580129cb

Source dataset

uspto-grants-1995_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05387599