886365-25-9

886365-22-6

General procedure for the synthesis of 2-methoxy-5-bromoisonicotinic acid from methyl 2-methoxy-5-bromopyridine-4-carboxylate: lithium hydroxide monohydrate (13.98 g, 333.25 mmol) and methyl 2-methoxy-5-bromopyridine-4-carboxylate (16.40 g, 66.65 mmol) were dissolved in tetrahydrofuran (30 mL) and water (6 mL) mixed solvent, and the reaction was stirred at 50 °C. After completion of the reaction, the mixture was cooled to 25 °C and kept for 2 hours. Subsequently, the reaction mixture was concentrated under reduced pressure. The concentrated aqueous phase residue was diluted with water (10 mL) and the pH was adjusted with 2M hydrochloric acid (80 mL) to 4. The mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product 5-bromo-2-methoxypyridine-4-carboxylic acid (9.62 g, 62% yield) as a brown oil. It was analyzed by liquid chromatography-mass spectrometry (LCMS) under the conditions of 5% to 95% aqueous acetonitrile (containing 0.03% trifluoroacetic acid), 1.5 min gradient elution, and the retention time was measured to be 0.448 min, and the measured [M+H]+ in ESI+ mode was 231.9.