反应详情

温度

30 °C

4-Bromoethylbenzene (s4) (30.0 g) and THF (1,000 ml) were placed in a reaction vessel under an atmosphere of nitrogen, and cooled to −74° C. n-Butyllithium (1.57M in n-hexane; 124 ml) was added dropwise in the temperature range of −74° C. to −70° C., and the stirring was continued for another 2 hours. 4-(1,4-Dioxaspiro[4.5]decan-8-yl)-cyclohexanone (s5) (38.6 g) in THF (200 ml) solution was added dropwise in the temperature range of −75° C. to −70° C., and the stirring was continued for another 8 hours while the mixture was allowed to come to 25° C. The resulting reaction mixture was poured into a vessel containing an aqueous solution of ammonium chloride (500 ml) and ethyl acetate (500 ml), and mixed with them. The mixture was allowed to stand and separate into organic and aqueous layers, and the latter was extracted. The separated organic layers were washed with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and dried over anhydrous magnesium sulfate. The solvent was distilled under reduced pressure. p-Toluenesulfonic acid (1.6 g) and toluene (300 ml) were added to the residue, and the mixture was heated to reflux for 2 hours, while distilled water was removed. After the reaction mixture had been cooled to 30° C., water (500 ml) and toluene (900 ml) were added and mixed with it. The mixture was allowed to stand and separate into two layers of organic and aqueous layers, and the latter was extracted. The organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The resulting solution was purified by fractionation using column chromatography with toluene as an eluent and silica gel as a stationary phase powder. The product was dissolved in a mixed solvent of toluene (250 ml) and Solmix A-11 (250 ml), to which Pd/C (0.3 g) was added. The mixture was stirred at room temperature under a hydrogen atmosphere until hydrogen absorption had ceased. After the reaction had been completed, Pd/C was removed, and then solvent was distilled off. The resulting residue was purified by fractionation using column chromatography with toluene as an eluent and silica gel as a stationary phase powder, and by recrystallization from heptane, and then dried to give 8-(trans-4-(4-ethylphenyl)cyclohexyl)-1,4-dioxaspiro[4.5]decane (s6) (33.2 g). The yield based on the compound (s1) was 62.3%.

1. additionwas added dropwise in the temperature range of −74° C. to −70° C.
2. waitthe stirring was continued for another 8 hours while the mixture
3. customto come to 25° C
4. customThe resulting reaction mixture
5. additionwas poured into a vessel
6. additionmixed with them
7. customseparate into organic and aqueous layers
8. extractionthe latter was extracted
9. washThe separated organic layers were washed with water
10. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and water, and dried over anhydrous magnesium sulfate
11. distillationThe solvent was distilled under reduced pressure
12. additionp-Toluenesulfonic acid (1.6 g) and toluene (300 ml) were added to the residue
13. temperaturethe mixture was heated
14. temperatureto reflux for 2 hours
15. distillationwhile distilled water
16. customwas removed
17. additionwater (500 ml) and toluene (900 ml) were added
18. additionmixed with it
19. customseparate into two layers of organic and aqueous layers
20. extractionthe latter was extracted
21. washThe organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate and water
22. dry with materialdried over anhydrous magnesium sulfate
23. customThe resulting solution was purified by fractionation
24. dissolutionThe product was dissolved in a mixed solvent of toluene (250 ml) and Solmix A-11 (250 ml), to which Pd/C (0.3 g)
25. additionwas added
26. customPd/C was removed
27. distillationsolvent was distilled off
28. customThe resulting residue was purified by fractionation
29. customsilica gel as a stationary phase powder, and by recrystallization from heptane
30. customdried