反应详情

2-Chloro-nicotinic acid ethyl ester, 4-fluoro-phenol, and cesium carbonate were mixed in anhydrous dioxane and the resulting slurry heated to reflux for about 16 h. In a separate flask, lithium hydroxide was dissolved in water with warming and then added to the refluxing mixture, which was heated for an additional 4 h. The mixture was cooled to ambient temperature and concentrated in vacuo to remove the dioxane. Concentrated hydrochloric acid was added dropwise until the pH=3. The acidified solution was then extracted with ethyl acetate to yield crude product, which was recrystallized from ethyl acetate to yield the purified title compound (10.8 g).

1. temperaturethe resulting slurry heated
2. temperatureto reflux for about 16 h
3. temperaturewith warming
4. additionadded to the refluxing mixture, which
5. temperaturewas heated for an additional 4 h
6. concentrationconcentrated in vacuo
7. customto remove the dioxane
8. additionConcentrated hydrochloric acid was added dropwise until the pH=3
9. extractionThe acidified solution was then extracted with ethyl acetate
10. customto yield crude product, which
11. customwas recrystallized from ethyl acetate
12. customto yield the
13. custompurified title compound (10.8 g)