General procedure for the synthesis of 2-bromo-4-chloro-3-methylpyridine from 2-bromo-4-chloropyridine and iodomethane: To a solution of 2,2,6,6-tetramethylpyridine (21.1 mL, 125 mmol) dissolved in freshly distilled tetrahydrofuran (THF, 120 mL) at -78 °C was added slowly over 30 min n-butyl lithium (nBuLi, 50 mL 125 mmol). The resulting mixture was stirred at -78 °C for 30 min. The above mixture was added to a solution of 3-bromo-4-chloropyridine (20.0 g, 104 mmol) dissolved in freshly distilled THF (60 mL) that had been cooled to -78 °C via cannula over 30 min. The reaction mixture was continued to be stirred at -78 °C for 30 min, followed by the addition of iodomethane (7.78 mL, 125 mmol) over 10 min. After stirring the reaction mixture at -78 °C for 30 min, it was slowly warmed to room temperature and the reaction was quenched with aqueous ammonium chloride (NH4Cl) (65 mL). The aqueous phase was extracted with ethyl acetate (2 x 150 mL). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated. The residue was purified by fast silica gel column chromatography (eluent: hexane/ethyl acetate, 5:1) to afford 2-bromo-4-chloro-3-methylpyridine as a yellow solid (10.6 g, 49% yield).1H NMR (CDCl3, 300 MHz) δ ppm: 8.10 (d, J = 5.1 Hz, 1H), 7.27 (d, J = 5.1 Hz, 1H) 2.51 (s, 3H).
