4.1.12 Synthesis of 5-bromopyridine-2-carboxylic acid (16): In a 250 mL three-necked flask equipped with a stirrer, thermometer, and condenser tube, 100 mL of water and 4-bromo-2-methylpyridine (15) (4.0 g, 23 mmol) were added. After the mixture was stirred and heated to 80 °C, potassium permanganate (KMnO4) (16.6 g, 105 mmol) was added in three batches at 1 h intervals. The reaction mixture was kept stirred at 80 °C for 3-4 hours. After completion of the reaction, the clarified filtrate was obtained by filtration. The pH of the filtrate was adjusted to 4-5 with concentrated hydrochloric acid (HCl), at which time a small amount of white solid was precipitated, which was a small amount of product (16). After filtration, the filtrate was concentrated in vacuum. To the concentrated residue, an appropriate amount of ethanol was added to dissolve the compound (16), at which time a large amount of white solid precipitated, which was removed by filtration. Finally, the filtrate was concentrated in vacuum to give a light yellow solid product (16) (1.70 g, 33% yield).
