General procedure for the synthesis of 4-bromo-2-fluoro-5-methylpyridine from 2-fluoro-3-bromo-5-methylpyridine: To a solution of 2-fluoro-3-bromo-5-methylpyridine (300 mg, 1.596 mmol) in tetrahydrofuran (THF, 10 mL) was added lithium diisopropylammonium (LDA, 2M, 0.8 mL) at -78°C and the reaction mixture was stirred at - 78 °C for 2 hours with stirring. Upon completion of the reaction, the reaction was quenched with 10 mL of water and extracted with ethyl acetate (EtOAc, 10 mL x 3). The organic phases were combined and concentrated to give the crude product. The crude product was purified by fast chromatography (normal phase, silica gel, petroleum ether: ethyl acetate = 0-100%, UV 254 and UV 280 detection) to afford 4-bromo-2-fluoro-5-methylpyridine (130 mg, 43% yield) as a yellow oil.1H-NMR (400 MHz, CDCl3) δppm: 2.37 (s, 3H), 7.19 (d 1H), 8.05 (s, 1H).
