[Synthesis]
Synthesis of 5-bromo-6-methoxypyridinecarboxylic acid: 5-bromo-6-chloropyridinecarboxylic acid (15.0 g, 63.4 mmol, 1.0 eq.) was suspended in methanol (130 mL) at room temperature, to which was added 4.37 M methanolic solution of sodium methanolate (58.0 mL, 253 mmol, 4.0 eq.). The reaction mixture was heated at 80 °C for 18 hours to form a thick mixture. Subsequently, the reaction mixture was diluted with methanol (100 mL) and stirring was continued at 80 °C for 24 hours. After completion of the reaction, the mixture was cooled to room temperature, acidified to pH=3 with concentrated aqueous hydrochloric acid, diluted with water and extracted with ethyl acetate (three times). The organic layers were combined, dried with magnesium sulfate, filtered and concentrated to give a residue. The residue was co-evaporated with dichloromethane/hexane (1:1 mixture, 200 mL, three times) to give the final 5-bromo-6-methoxypyridine carboxylic acid (13.9 g, 94% yield) as a white solid.1H NMR (500 MHz, CDCl3) δ 10.22 (br s, 1H), 8.06 (d, J = 7.7 Hz, 1H), 7.73 (d, J = 7.7 Hz, 1H), 4.10 (s, 3H).LCMS (ES-) [M-H]-: 229.9/231.9. |