2-Chloro-3-fluoro-5-methylpyridine (512 mg, 3.5 mmol) was used as starting material and dissolved in a solvent mixture of pyridine (2.5 mL) and water (2.5 mL). Potassium permanganate (1.1 g, 6.9 mmol) was added to this solution in batches and after the first addition, the reaction mixture was heated to 100 °C and stirred for 1 hour. Subsequently, additional potassium permanganate (totaling 3.3 g, 20.7 mmol) was added in two batches over a period of 2 hours. During the reaction, if solids accumulate in the condenser, it can be washed with water and pyridine. After continued stirring at 100 °C for 1 h, the reaction mixture was cooled to room temperature. The reaction was quenched with saturated aqueous Na2S2O3 and stirred for 30 minutes. The reaction mixture was filtered and the filtrate was acidified to pH 2 with 1.5 M HCl. The aqueous phase was extracted with EtOAc (3×), the organic phases were combined and washed with brine (1×), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by rapid chromatography on silica gel, using a gradient elution of 90% to 70% petroleum ether-EtOAc to afford 5-fluoro-6-chloronicotinic acid as a white solid (300 mg, 49% yield).
