(2) Synthesis of 3-bromo-2-methoxy-4-methylpyridine: In a dry reaction flask, 3-bromo-2-chloro-4-methylpyridine (1 g) was dissolved in N,N-dimethylformamide (DMF, 5.6 mL). Subsequently, sodium methanol (28% methanol solution, 4.6 mL) was slowly added to this solution. The reaction mixture was placed in an oil bath at 100°C and the reaction was stirred for 12 hours. After completion of the reaction, the mixture was cooled to room temperature and liquid-liquid partitioned with ethyl acetate and water. The organic layer was separated and dried with anhydrous magnesium sulfate. After filtration to remove the drier, the filtrate was concentrated under reduced pressure to give the crude product. The crude product was further purified by silica gel column chromatography with the eluent of ethyl acetate/n-heptane (gradient elution, 5% to 30%) to afford the target compound 3-bromo-2-methoxy-4-methylpyridine (1.1 g). The structure of the product was confirmed by 1H-NMR (400 MHz, CDCl3): δ (ppm) 2.40 (s, 3H, CH3), 4.00 (s, 3H, OCH3), 6.77 (d, J = 5.1 Hz, 1H, pyridine ring H), 7.94 (d, J = 5.1 Hz, 1H, pyridine ring H).
