反应详情

To a solution of benzyl alcohol (22.0 mL) in DMF (100 mL) was added sodium hydride (60% oil, 8.52 g), and the mixture was stirred at room temperature for 15 min. To the reaction mixture was added 3,4,5-trifluorobenzoic acid (15.0 g), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was neutralized with 6 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To a solution of the obtained residue in DMF (100 mL) were added potassium carbonate (11.8 g) and methyl iodide (5.30 mL), and the mixture was stirred with heating at 60° C. for 15 min. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate). To a solution of the obtained oil in a mixed solvent of THF (100 mL) and methanol (50 mL) was added 2 M aqueous sodium hydroxide solution (85 mL), and the mixture was stirred with heating at 60° C. for 40 min. The reaction mixture was allowed to cool to room temperature, and neutralized with 6 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained solid was washed with diethyl ether/hexane to give the title compound (18.2 g).

1. stirringthe mixture was stirred at room temperature for 1 hr
2. extractionthe mixture was extracted with ethyl acetate
3. washThe obtained organic layer was washed with saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. customthe solvent was evaporated under reduced pressure
6. additionTo a solution of the obtained residue in DMF (100 mL) were added potassium carbonate (11.8 g) and methyl iodide (5.30 mL)
7. stirringthe mixture was stirred
8. temperaturewith heating at 60° C. for 15 min
9. temperatureto cool to room temperature
10. additiondiluted with ethyl acetate
11. washwashed with saturated brine
12. dry with materialdried over anhydrous magnesium sulfate
13. customThe solvent was evaporated under reduced pressure
14. customthe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)
15. additionTo a solution of the obtained oil in a mixed solvent of THF (100 mL) and methanol (50 mL) was added 2 M aqueous sodium hydroxide solution (85 mL)
16. stirringthe mixture was stirred
17. temperaturewith heating at 60° C. for 40 min
18. temperatureto cool to room temperature
19. extractionthe mixture was extracted with ethyl acetate
20. washThe obtained organic layer was washed with saturated brine
21. dry with materialdried over anhydrous magnesium sulfate
22. customthe solvent was evaporated under reduced pressure
23. washThe obtained solid was washed with diethyl ether/hexane