反应详情

温度

80 °C

To 570 mg (0.741 mmol) of 2-[4-((5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-2-yl)piperidin-1-yl]pyrimidin-5-ol, which was prepared by a method similar to that of Reference Example 14, 288 mg (1.11 mmol) of 3-hydroxy-3-methylbutyl toluenesulfonate and 198 mg (1.43 mmol) of potassium carbonate, 2 ml of N,N-dimethylformamide was added, and the reaction mixture was stirred at 80° C. for 2.8 hours. After completion of the reaction, toluene and water were added to the reaction solution to separate an organic phase. Further, the reaction mixture was extracted with toluene from the aqueous phase. The obtained organic phases were combined and washed with saturated sodium chloride aqueous solution, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography [n-hexane/ethyl acetate=78/22-50/50 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure. The obtained residue was dissolved in ethyl acetate, then n-heptane was added thereto, and the precipitate was obtained by filtration to provide 455 mg of the title compound as a white solid (yield: 72%).

1. additionwas added
2. additionwere added to the reaction solution
3. customto separate an organic phase
4. extractionFurther, the reaction mixture was extracted with toluene from the aqueous phase
5. washwashed with saturated sodium chloride aqueous solution
6. distillationthe solvent was distilled off under reduced pressure
7. concentrationwas concentrated under reduced pressure
8. dissolutionThe obtained residue was dissolved in ethyl acetate
9. additionn-heptane was added
10. customthe precipitate was obtained by filtration