N-Bromosuccinimide (11.88 g, 84.91 mmol) was added to a solution of 2,3-dimethoxypyrazine (8.5 g, 60.71 mmol) in N,N-dimethylformamide (85 mL) under nitrogen protection. The reaction mixture was stirred at room temperature for 48 hours. Upon completion of the reaction, the mixture was cooled to -40°C and subsequently slowly poured into a 1.0 N aqueous solution of Na2S2O3. The resulting mixture was continued to be stirred at 0°C for 30 minutes. The reaction mixture was collected as a solid product by filtration and washed with deionized water. The crude product was further purified by silica gel column chromatography with the eluent ethyl acetate/hexane (0-2% gradient) to afford 5-bromo-2,3-dimethoxypyrazine (6.0 g, 45% yield). The product was analyzed by LC-MS showing m/z of 219.0 [M + H]+ and 1H NMR (400 MHz, CDCl3) data as follows: δ 7.71 (s, 1H), 4.01 (d, J = 14.0 Hz, 6H).
