A solution of 2,5-dibromo-4-methylpyridine (2.51 g, 10.0 mmol) in anhydrous THF (50 mL) was added to a three-necked flask, followed by tetrakis(triphenylphosphine)palladium (1.15 g, 1.0 mmol). The reaction mixture was cooled to 0 °C under nitrogen protection and stirred. A THF solution of methylmagnesium bromide (15 mL, 15.0 mmol, 1 mol/L) was added slowly and dropwise. After the dropwise addition, the reaction mixture was heated to reflux for 3 hours. After completion of the reaction, it was cooled to room temperature, the reaction was quenched with 1N hydrochloric acid and extracted with ethyl acetate (100 mL x 3). The organic layers were combined, washed sequentially with water (50 mL x 2) and saturated saline (50 mL) and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the crude product was purified by Biotage fast chromatography (petroleum ether/ethyl acetate = 5%-10%) to afford 2,4-dimethyl-5-bromopyridine (301 mg, 16.2%) as a colorless oil.1H NMR (400 MHz, CDCl3) δppm: 2.35 (d, 3H), 2.47 (s, 3H), 7.04 ( s, 1H), 8.50 (s, 1H).
