反应详情

温度

100 °C

To a mixture of 3-[chloro(cyclohexyl)methyl]-2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophene (1.00 g) synthesized above, methyl 4-aminobenzoate (780 mg), sodium iodide (1.55 g) and N,N-dimethylacetamide (10 mL) was added sodium carbonate (547 mg), and the mixture was stirred under an argon atmosphere at 100° C. overnight. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give a dark-brown oil. To a mixture of the obtained oil, tetrahydrofuran (10 mL) and ethanol (10 mL) was added 1N aqueous sodium hydroxide solution (10 mL), and the mixture was stirred at 60° C. for 1 hr, and stirred with heating under reflux for 30 min. 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=3:7, volume ratio) to give a brown oil. The obtained oil was dissolved in ethyl acetate, washed with 1N hydrochloric acid and brine, dried over magnesium sulfate and concentrated under reduced pressure to give the title compound (369 mg, 29%) as a pale-brown solid.

1. customto quench
2. customthe reaction
3. extractionthe mixture was extracted with ethyl acetate
4. washThe extract was washed with brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customto give a dark-brown oil
8. stirringthe mixture was stirred at 60° C. for 1 hr
9. stirringstirred
10. temperaturewith heating
11. temperatureunder reflux for 30 min
12. customthe organic solvent was evaporated under reduced pressure
13. extractionthe mixture was extracted with ethyl acetate
14. washThe extract was washed with brine
15. dry with materialdried over magnesium sulfate
16. concentrationconcentrated under reduced pressure
17. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:7, volume ratio)
18. customto give a brown oil
19. washwashed with 1N hydrochloric acid and brine
20. dry with materialdried over magnesium sulfate
21. concentrationconcentrated under reduced pressure