Synthesis
General procedure for the synthesis of 6-bromo-3-methoxy-2-pyridinecarboxylic acid from methyl 6-bromo-3-methoxypyridinecarboxylate: Methyl 6-bromo-3-methoxypyridinecarboxylate (4 g, 18.4 mmol) and lithium hydroxide monohydrate (LiOH-H2O, 1.6 g, 36.9 mmol) were reacted in a solvent mixture of dioxane/water (5:1, 40 mL) at room temperature. The reaction was stirred overnight at room temperature. After completion of the reaction, the pH of the reaction solution was adjusted to 7 with dilute hydrochloric acid, and the precipitate was collected by filtration to afford the crude product 6-bromo-3-methoxy-2-pyridinecarboxylic acid (3.1 g, yield: 81%). The product was confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H NMR, CDCl3, 400 MHz): δ 10.71 (m, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 4.01 (s, 3H). Mass spectrometry (MS) analysis showed the molecular ion peak (M + H)+: 232/234.
References
[1] Patent: WO2014/121418, 2014, A1. Location in patent: Page/Page column 45
[2] Patent: WO2007/31558, 2007, A1. Location in patent: Page/Page column 32
[3] Patent: WO2014/209727, 2014, A1. Location in patent: Page/Page column 39-40
[4] Patent: WO2014/205593, 2014, A1. Location in patent: Page/Page column 42
