反应详情

温度

40 °C

First Step: 6.1 g of well dried magnesium and 20 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 40° C. 59.7 g of 1-bromo-4-ethoxy-2,3-difluorobenzene (1) dissolved in 300 mL of THF was slowly added dropwise thereto at a temperature range of from 40 to 60° C., followed by stirring for 60 minutes. Thereafter, 50.0 g of 4-(1,4-dioxaspiro[4,5]dec-8-yl)cyclohexanone (2) dissolved in 150 mL of THF was slowly added dropwise thereto at a temperature range of from 50 to 60° C., followed by stirring for 60 minutes. After cooling the resulting reaction mixture to 30° C., the reaction mixture was mixed with 900 mL of a 3% ammonium chloride aqueous solution and 500 mL of toluene cooled to 0° C. in a vessel and separated into an organic layer and an aqueous layer by standing still, so as to attain extraction. The resulting organic layer was fractionated and washed with water, a saturated sodium bicarbonate aqueous solution, and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was distilled off under reduced pressure to obtain 100.1 g of 4-(1,4-dioxaspiro[4,5]dec-8-yl)-1-(4-ethoxy-2,3-difluorophenyl)cyclohexanol (3). The resulting compound (3) was a yellow solid.

1. additionwas slowly added dropwise
2. customof from 40 to 60° C.
3. additionwas slowly added dropwise
4. customof from 50 to 60° C.
5. stirringby stirring for 60 minutes
6. temperatureAfter cooling
7. customthe resulting reaction mixture to 30° C.
8. temperaturecooled to 0° C. in a vessel
9. customseparated into an organic layer
10. extractionextraction
11. washwashed with water
12. dry with materialby drying over anhydrous magnesium sulfate
13. distillationThereafter, the solvent was distilled off under reduced pressure