3-Fluoro-4-methylbenzoic acid

white to light yellow crystal powder

3-Fluoro-4-toluic Acid was used in the synthesis of cyclooxygenase selective and orally active antiinflammatory agents. It was also used to prepare benzamide derivatives as Bcr-Abl kinase inhibitors.

In a Schlenk (50 mL) reaction flask with a carbon dioxide balloon attached at the stub, Cu(OAc)2.H2O (0.0125 mmol), 1,2-bis(diphenylphosphino)benzene (0.018 mmol), and 1,4-dioxane (2.0 mL) were added with stirring, and then the flask was placed at 60 C oil bath for 25 min under carbon dioxide atmosphere, followed by the sequential addition of toluene (8 mL), 3-fluoro-4-methylbromobenzene (1.0 mmol), Pd(OAc)2 (0.03 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthene (0.06 mmol), Et3N (2.5 mmol, 2.5 equiva. ), then carbon dioxide was removed and the reaction was carried out at 100 C until the raw material bromobenzene disappeared, cooled to room temperature and sodium hydroxide solution (1M, 10.0 mL) was added, stirred for 10 min and filtered, the solids were washed with water three times, the filtrate was extracted with ethyl acetate (2 10 mL) leaving an aqueous layer, the aqueous layer was adjusted to pH 1-2 with hydrochloric acid solution (1M), ethyl acetate (3 15 mL ) was extracted with ethyl acetate (315 mL), dried with anhydrous sodium sulfate, and the solvent was removed to obtain 3-fluoro-4-methylbenzoic acid in 84% yield.