反应详情

In a reactor under nitrogen atmosphere, 20 mL of ethanol and 0.4 g of sodium cyanoborohydride were added to 5.4 g of ethyl 4-[4-(4-ethoxy-2,3-difluorophenoxymethyl)cyclohexyl]5-oxopentanoate obtained in the eleventh step, and pH of the mixture was adjusted to about 3 with hydrochloric acid (2M), followed by stirring at room temperature for 15 hours. 30 mL of water was added to the reaction solution, which was extracted three times with 20 mL of toluene. The mixture including the organic layer was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was placed in a flask equipped with a Dean-Stark apparatus, to which 100 mL of toluene and 0.1 g of p-toluenesulfonic acid monohydrate were added, and the mixture was refluxed for 1 hour while the solvent was distilled off with the Dean-Stark apparatus. The solution was cooled to room temperature, washed with water, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to provide 4.5 g of 5-[4-(4-ethoxy2,3-difluorophenoxymethyl)cyclohexyl]tetrahydropyran-2-one.

1. customobtained in the eleventh step, and pH of the mixture
2. extractionwas extracted three times with 20 mL of toluene
3. washwas washed with water
4. dry with materialdried over anhydrous magnesium sulfate
5. distillationthe solvent was distilled off under reduced pressure
6. customThe residue was placed in a flask
7. customequipped with a Dean-Stark apparatus, to which 100 mL of toluene and 0.1 g of p-toluenesulfonic acid monohydrate
8. additionwere added
9. temperaturethe mixture was refluxed for 1 hour while the solvent
10. distillationwas distilled off with the Dean-Stark apparatus
11. temperatureThe solution was cooled to room temperature
12. washwashed with water
13. dry with materialdried over anhydrous magnesium sulfate
14. distillationthe solvent was distilled off under reduced pressure
15. customThe residue was purified by silica gel column chromatography