反应详情

50 g of 3-(4-chloro-2-fluorophenyl)-5-hydroxy-1H-pyrazole from Example 1.1 were initially charged in 1500 ml of toluene. 35.5 g of dimethyl sulfate were then added, and the mixture was heated at reflux for 3 h. After cooling to room temperature, the mixture was made alkaline using ammonia, stirred overnight and acidified by addition of hydrochloric acid. The mixture was then cooled to 0° C., and the precipitated solid was filtered off. After drying, 49.4 g of 3-(4-chloro-2-fluorophenyl)-5-hydroxy-1-methyl-1H-pyrazole were obtained as crude product (purity according to NMR about 80%, impurity essentially starting material), which was purified by recrystallization from toluene to >95% purity. Yield 49.4 g, 74.1%. M.p.: 204° C.

1. temperaturethe mixture was heated
2. temperatureat reflux for 3 h
3. temperatureThe mixture was then cooled to 0° C.
4. filtrationthe precipitated solid was filtered off
5. customAfter drying