反应详情

64 g of the 3-(4-chloro-2-fluorophenyl)-5-hydroxy-1H-pyrazole obtained in step 1.1 were initially charged in 600 ml of dioxane. A solution of 24 g of sodium hydroxide in 70 ml of water was added, and the mixture was heated at reflux. With stirring, 238.7 g (2.76 mol, 9.2 eq.) of gaseous chlorodifluoromethane were added, and during the addition the pH was monitored constantly and, when it approached the neutral range (pH<9), increased by addition of additional NaOH solution to about pH 12. After 6 h, the mixture was allowed to cool, 1800 ml of water were added and the mixture was extracted twice with in each case 500 ml of MTBE. The combined organic phases were washed with in each case 500 ml of water and saturated sodium chloride solution, dried over Na2SO4, filtered and concentrated. This gave 58.7 g of crude 3-(4-chloro-2-fluorophenyl)-5-difluoromethoxy-1H-pyrazole. 32.3 g of this mixture were distilled under reduced pressure, giving 11.6 g of the title compound as an oil of a purity of 86%. Yield: 22.9%

1. temperaturethe mixture was heated
2. temperatureat reflux
3. additionduring the addition the pH
4. temperatureto cool
5. extractionthe mixture was extracted twice with in each case 500 ml of MTBE
6. washThe combined organic phases were washed with in each case 500 ml of water and saturated sodium chloride solution
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. distillation32.3 g of this mixture were distilled under reduced pressure