67-56-1

316808-10-3

316808-11-4

Concentrated hydrochloric acid was slowly added to a stirred solution of 3-bromopyridine-2,6-dicarboxylic acid (20.0 kg, 81.29 mol) in methanol (100 L). Subsequently, sulfuric acid (4.4 L) was added dropwise over 30 min. The reaction mixture was heated to 65 °C and maintained at this temperature for 5 h (reaction progress was monitored by TLC). Upon completion of the reaction, the mixture was cooled to room temperature and alkalized by careful addition of an aqueous NaHCO3 solution prepared from sodium bicarbonate (10 kg) and water (120 L) and further diluted with water (120 L). The resulting white solid was collected by filtration, washed with plenty of water and subsequently oven dried at 40 °C to afford dimethyl 3-bromopyridine-2,6-dicarboxylate (9.2 kg, 41.3% yield) as a white solid.1HNMR (300 MHz, DMSO-d6) δ 8.47 (d, J = 8.4 Hz, 1H), 8.08 (dd, J = 4.5, 8.4 Hz, 1H), 3.95 (s, 3H), 3.91 (s, 3H); MS (ES+) m/z 570.6 (2M + Na)+; Elemental analysis (C9H8BrNO4) Calculated value: C, 39.44; H, 2.94; Br, 29.15; N, 5.1; Measured value: C, 39.52; H, 2.92; Br, 29.28; N, 5.03.