General procedure for the synthesis of 5-bromo-2-methoxynicotinic acid from 2-methoxynicotinic acid: 2-methoxynicotinic acid (20 g, 130.60 mmol) was dissolved in H2O (1500 mL) at room temperature, followed by slow addition of Br2 (20 mL, 375.45 mmol). The reaction mixture was stirred continuously at room temperature overnight. Upon completion of the reaction, the solid product was collected by filtration and washed thoroughly with deionized water and finally dried to afford 5-bromo-2-methoxynicotinic acid (25 g, 82% yield). The structure of the product was confirmed by 1H-NMR (DMSO-d6, 400 MHz) and mass spectrometry (MS): 1H-NMR δ 13.33 (br s, 1H), 8.47 (d, J = 2.4 Hz, 1H), 8.21 (d, J = 2.4 Hz, 1H), 3.90 (s, 3H); MS (M + H)+ m/z: 232/234.
