General procedure for the synthesis of methyl 2-methoxynicotinate from methanol and 2-methoxynicotinic acid:
a) Synthesis of methyl 2-methoxynicotinate: a concentrated aqueous sulfuric acid solution (0.1 mL) was slowly added to a solution of methanol (20 mL) containing 2-methoxynicotinic acid (2.00 g, 13.1 mmol), stirred to mix well and then heated to reflux. After the reaction was carried out for 6 hours, saturated aqueous sodium bicarbonate solution was added to the reaction mixture for neutralization, followed by extraction with ethyl acetate. The organic layer was separated, dried with anhydrous magnesium sulfate and concentrated under reduced pressure to afford the target product methyl 2-methoxynicotinate (1.85 g, 85% yield) as a colorless oil. Low resolution mass spectrometry (LRMS) showed m/z: 168 ([M + 1]+).1H NMR (300 MHz, DMSO-d6) δ ppm: 3.81 (s, 3H), 3.92 (s, 3H), 7.11 (dd, 1H), 8.13 (dd, 1H), 8.38 (dd, 1H).
