4-Fluorophenol → 2-(4-Fluorophenoxy)nicotinic acid

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Reaction Steps

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).

Provenance & Evidence