反应详情

温度

-30 °C

To a solution of diisopropylamine (11 g) in dry THF (100 ml) 1.6 M solution of butyllithium in hexane (63 ml) was slowly added at −78° C. under nitrogen atmosphere. The mixture was allowed to warm up to −30° C., then re-cooled to −78° C. before propionitrile (5.4 g) was slowly added (exothermic reaction, cooling). The mixture was stirred at this temperature for ca. 15 min, 1-(2,5-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone (10 g) was added, the reaction mixture warmed up to −20° C. within ca. 1 hr and finally poured on aqueous solution of phosphate buffer (pH 7). The aqueous phase was extracted 3 times with ethylacetate (300 ml) and the combined organic phase was twice with water, dried with sodium carbonate, filtered and evaporated under reduced pressure providing the title compound: 9 g. The analytical data were identical with published in U.S. Pat. No. 6,300,353 and WO99/45008 for (2S,3R)-enantiomer.

1. additionwas slowly added
2. custom(exothermic reaction, cooling)
3. temperaturethe reaction mixture warmed up to −20° C. within ca. 1 hr
4. extractionThe aqueous phase was extracted 3 times with ethylacetate (300 ml)
5. dry with materialdried with sodium carbonate
6. filtrationfiltered
7. customevaporated under reduced pressure