3-Amino-2-bromo-4-methoxypyridine

33631-09-3

109613-97-0

General procedure for the synthesis of 3-amino-2-bromo-4-methoxypyridine from 3-amino-4-methoxypyridine: To a concentrated solution of 3-amino-4-methoxypyridine (6.76 g, 54.5 mmol) in hydrochloric acid (50 mL), bromine (3.36 mL, 65.4 mmol) was added dropwise over a period of 30 seconds. The reaction mixture was stirred at room temperature for 1 hour and subsequently heated at 55 °C overnight. Upon completion of the reaction, the mixture was cooled to room temperature and poured into ice water. The pH of the solution was adjusted to alkaline with ammonium hydroxide. The resulting suspension was partitioned between water and ethyl acetate. The organic and aqueous layers were separated and the aqueous layer was extracted with ethyl acetate (2×). The organic layers were combined, washed sequentially with water and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent ethyl acetate/methanol (100/0 to 80/20) to afford 9.18 g of the target product in white powder form (82% yield). Product characterization data: 1H NMR (CDCl3, 300 MHz) δ 7.75 (d, J = 5.3 Hz, 1H), 6.68 (d, J = 5.3 Hz, 1H), 3.91 (s, 3H); LC Rt: 0.89 min; LCMS m/z 203 ([M+H]+, 100%).