反应详情

温度

-70 °C

In a reactor under nitrogen atmosphere, 100 mL of THF was added to 4.5 g of 5-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]tetrahydropyran-2-one obtained in the twelfth step, and the mixture was cooled to −70° C., to which 15 mL of n-propyllithium (about 1.0 mmol) was added dropwise. After stirring the mixture at −70° C. for 1 hour, the temperature of the reaction mixture was increased to room temperature, and 50 mL of a saturated ammonium chloride aqueous solution was added thereto, followed by separating. The aqueous layer was extracted three times with 30 mL of diethyl ether, and the mixture including the organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by distilling off the solvent under reduced pressure. The residue was purified by silica gel column chromatography to provide 3.6 g of 5-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]2-propyltetrahydropyran-2-ol.

1. customobtained in the twelfth step
2. additionwas added dropwise
3. temperaturethe temperature of the reaction mixture was increased to room temperature
4. customby separating
5. extractionThe aqueous layer was extracted three times with 30 mL of diethyl ether
6. washwas washed with water
7. dry with materialdried over anhydrous magnesium sulfate
8. distillationby distilling off the solvent under reduced pressure
9. customThe residue was purified by silica gel column chromatography