1H-1,2,4-Triazole → (2R,3S)-2-(2,3-Difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane

3.32 g (48.1 mmol) of 1H-1,2,4-triazole were added to a suspension of 1.84 g (41.1 mmol) of a 55% dispersion of sodium hydride in oil in 30 ml of N,N-dimethylformamide at 0° C. with stirring. After the evolution of hydrogen gas had ceased, a solution of 4.50 g (12 mmol) of (2R,3R)-2-(2,3-difluorophenyl)-1,3-bis(methanesulfonyloxy)-2-butanol [prepared as described in Step 7 (iii) above] in 13 ml of N,N-dimethylformamide was added to the above reaction mixture. This resulting mixture was stirred at 70° C. for 1.5 hours. After cooling. a saturated aqueous ammonium chloride solution was added to the reaction mixture. The reaction product was extracted with ethyl acetate and the organic layer was washed with water three times and with aqueous sodium chloride solution once and then concentrated under reduced pressure. The resulting residue was purified by chromatographv on a silica gel (100 g) column using a 1:1 mixture of ethyl acetate and hexane as the eluant to afford 1.80 g (yield 59%) of the title compound as an oil.

1. stirringThis resulting mixture was stirred at 70° C. for 1.5 hours
2. temperatureAfter cooling
3. extractionThe reaction product was extracted with ethyl acetate
4. washthe organic layer was washed with water three times and with aqueous sodium chloride solution once
5. concentrationconcentrated under reduced pressure
6. customThe resulting residue was purified by chromatographv on a silica gel (100 g) column
7. additiona 1:1 mixture of ethyl acetate and hexane as the eluant

ORD record

ord-3b7368b3f63f44888e6b8d67530a641f

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06392082B1