反应详情

To a mixture of cyclohexyl{2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophen-3-yl}methanol (648 mg) synthesized above, methyl 4-hydroxybenzoate (321 mg), 1,1′-(azodicarbonyl)dipiperidine (888 mg) and tetrahydrofuran (20 mL) was added tributylphosphine (877 μL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, the precipitate was removed by filtration, and washed with diisopropyl ether. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9, volume ratio) to give a yellow oil. To a mixture of the obtained oil, tetrahydrofuran (10 mL) and ethanol (10 mL) was added 2N aqueous sodium hydroxide solution (5 mL), and the mixture was stirred at 50° C. for 2 hr. 1N Hydrochloric acid (10 mL) was added to the reaction mixture, the organic solvent was evaporated under reduced pressure, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4, volume ratio) to give the title compound (413 mg, 85%) as a white solid.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. customthe precipitate was removed by filtration
3. washwashed with diisopropyl ether
4. concentrationThe filtrate was concentrated under reduced pressure
5. customthe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9, volume ratio)
6. customto give a yellow oil
7. stirringthe mixture was stirred at 50° C. for 2 hr
8. customthe organic solvent was evaporated under reduced pressure
9. extractionthe mixture was extracted with ethyl acetate
10. washThe extract was washed with brine
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated under reduced pressure
13. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4, volume ratio)