C1COCC1.[Br-].[F:7][CH2:8][CH2:9][CH2:10]P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[K+].[F:36][C:37]1[CH:38]=[C:39]([CH:44]2[CH2:49][CH2:48][C:47](=O)[CH2:46][CH2:45]2)[CH:40]=[C:41]([F:43])[CH:42]=1>O>[F:36][C:37]1[CH:38]=[C:39]([CH:44]2[CH2:49][CH2:48][CH:47]([CH2:10][CH2:9][CH2:8][F:7])[CH2:46][CH2:45]2)[CH:40]=[C:41]([F:43])[CH:42]=1THF (60 ml) was added to 3-fluoropropyltriphenylphosphinebromide (10.3 g, 25.5 mmol) prepared at the second step of Example 1, followed by cooling the mixture down to -50° C. in nitrogen atmosphere, adding to the mixture, a 40 ml THF solution of potassium-t-butoxide (2.86 g, 25.5 mmol), stirring the mixture at the same temperature for 3 hours, dropwise adding to the reaction solution, a 100 ml THF solution of 4-(3,5-difluorophenyl)cyclohexanone (43.8 g, 20.8 mmol) prepared at the first step, stirring the mixture at the same temperature for one hour, stirring at room temperature for 3 hours, adding water (200 ml) to the reaction solution, extracting the resulting product with ethyl acetate, washing the organic layer successively with a saturated aqueous solution of sodium bicarbonate and water, drying over magnesium sulfate, purifying an yellow solution obtained by distilling off the solvent, according to column chromatography treatment using toluene as a developing solvent, on silica gel, hydrogenating the resulting cyclohexylidene derivative using a catalyst of Pd/C, in ethanol, filtering off the catalyst after the reaction, distilling off ethanol under reduced pressure and recrystallizing the resulting product using a mixed solvent of heptane with ethanol, to obtain 4-(3,5-difluorophenyl)-1-(3-fluoropropyl)cyclohexane (1.50 g, 6.14 mmol). Yield: 29.5%.
読み込み中…
