[Synthesis]
General procedure for the synthesis of 2-bromo-5-methoxy-4-methylaniline from sodium bicarbonate and 3-methoxy-4-methylaniline: to a solution of 3-methoxy-4-methylaniline (8.19 g, 59.71 mmol) in dichloromethane (200 mL) was added tetrabutylammonium tribromide (28.79 g, 59.71 mmol) and the reaction mixture was stirred at room temperature for 2.5 hours. Upon completion of the reaction, aqueous sodium bicarbonate was added for neutralization and the organic layer was separated. The aqueous layer was further extracted with dichloromethane, and the organic phases were combined, washed sequentially with water and brine, dried with anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane solution of 20% ethyl acetate) to afford 11.05 g of 2-bromo-5-methoxy-4-methylaniline in 85% yield. The product was characterized by 1H NMR (300 MHz, CDCl3): δ 2.09 (s, 3H), 3.75 (s, 3H), 3.95 (br s, 1H), 6.27 (s, 1H), 7.13 (s, 1H). |