6-(4-Fluorophenyl)-nicotinic acid

149500-84-5

223127-24-0

General procedure for the synthesis of 6-(4-fluorophenyl)nicotinic acid from methyl 6-(4-fluorophenyl)nicotinate: first, methyl 6-bromopyridine-3-carboxylate (1.03 g, 4.78 mmol), 4-fluorophenylboronic acid (1.88 g, 13.41 mmol), and cesium fluoride (2.55 g, 16.78 mmol) were stirred together in a mixture of N,N-dimethylformamide (DMF , 25 mL) and deionized water (4 mL) in a solvent mixture was stirred and mixed. The reaction mixture was placed in an oil bath at 80 °C and reacted in air. After heating for 5 min, palladium acetate (Pd(OAc)2, 150 mg, 0.67 mmol) was added all at once. After 17 hours of reaction, the solution was cooled to room temperature, diluted with ethyl acetate and filtered through a short column of diatomaceous earth. The organic phase was washed with deionized water, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated. Purification by fast column chromatography afforded methyl 6-(4-fluorophenyl)pyridine-3-carboxylate as a yellow solid. Subsequently, the purified ester was dissolved in tetrahydrofuran (THF, 0.25 M) and an equal volume of 1 M sodium hydroxide (NaOH) solution was added. The reaction was stirred vigorously for 15 h at room temperature. After completion of the reaction, it was acidified with concentrated hydrochloric acid (HCl) to pH < 2. The precipitated white precipitate was collected by filtration. After vacuum drying, 385 mg of 6-(4-fluorophenyl)nicotinic acid was obtained in 37% yield. Mass spectrum (electrospray ionization, ES): m/z 218.1 ([M+H]+).