Hydrochloric Acid → (5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-(1-{5-[3-hydroxy-2-(hydroxymethyl)propoxy]pyrimidin-2-yl}piperidin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydr oquinolin-5-ol

温度

80 °C

To a solution of 8.42 g (9.39 mmol) of (5S)-4-(4,4-Difluorocyclohexyl)-2-(1-{5-[(2,2-dimethyl-1,3-dioxan-5-yl)methoxy]pyrimidin-2-yl}piperidin-4-yl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 21, in 75 ml of 1,4-dioxane, 15 ml of 6 N hydrochloric acid was added, and the reaction mixture was stirred at 80° C. for 2 hours. After completion of the reaction, the reaction solution was poured into a mixed solution of saturated sodium hydrogencarbonate aqueous solution and 2 N sodium hydroxide aqueous solution and extracted with ethyl acetate three times. The obtained organic phases were combined, washed with saturated sodium chloride aqueous solution and dried with anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography [n-hexane/ethyl acetate=60/40-30/70 (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 5.72 g of the title compound as a white solid (yield: 83%).

1. customAfter completion of the reaction
2. extractionextracted with ethyl acetate three times
3. washwashed with saturated sodium chloride aqueous solution
4. dry with materialdried with anhydrous magnesium sulfate
5. distillationthe solvent was distilled off under reduced pressure
6. concentrationwas concentrated under reduced pressure
7. dissolutionThe obtained residue was dissolved in ethyl acetate
8. additionn-heptane was added
9. customthe precipitate was obtained by filtration

ORDレコード

ord-e0f0651640644e5e9506fe16ea72d402

出典データセット

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09321747B2