反应详情

温度

70 °C

To a solution of 3-fluoro-4-hydroxybenzoic acid (25.0 g) in methanol (150 mL) was added sulfuric acid (20.0 mL), and the mixture was heated under reflux for 1 day. To the reaction mixture was added saturated brine, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To a solution of the obtained residue in DMF (200 mL) were added potassium carbonate (33.2 g) and benzyl bromide (21.0 mL), and the mixture was stirred with heating at 70° C. for 30 min. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate, and washed with saturated brine. The obtained organic layer was subjected to silica gel column chromatography (NH, ethyl acetate), and the solvent was evaporated. To a solution of the obtained residue in a mixed solvent of THF (100 mL) and methanol (100 mL) was added 2 M aqueous sodium hydroxide solution (160 mL), and the mixture was stirred with heating at 50° C. for 2 hr. 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 ethyl acetate to give the title compound (36.3 g).

1. temperaturethe mixture was heated
2. temperatureunder reflux for 1 day
3. extractionthe mixture was extracted with ethyl acetate
4. dry with materialThe obtained organic layer was dried over anhydrous magnesium sulfate
5. customthe solvent was evaporated under reduced pressure
6. additionTo a solution of the obtained residue in DMF (200 mL) were added potassium carbonate (33.2 g) and benzyl bromide (21.0 mL)
7. temperatureto cool to room temperature
8. additiondiluted with ethyl acetate
9. washwashed with saturated brine
10. customthe solvent was evaporated
11. additionTo a solution of the obtained residue in a mixed solvent of THF (100 mL) and methanol (100 mL) was added 2 M aqueous sodium hydroxide solution (160 mL)
12. stirringthe mixture was stirred
13. temperaturewith heating at 50° C. for 2 hr
14. temperatureto cool to room temperature
15. extractionthe mixture was extracted with ethyl acetate
16. washThe obtained organic layer was washed with saturated brine
17. dry with materialdried over anhydrous magnesium sulfate
18. customthe solvent was evaporated under reduced pressure
19. washThe obtained solid was washed with ethyl acetate