The general procedure for the synthesis of 5-(methoxycarbonyl)-2-pyridinecarboxylic acid from methyl 2,5-pyridinedicarboxylate was as follows: 5-methyl 2,5-pyridinedicarboxylate (28 g, 0.146 mol) was placed in a 500 mL three-necked, round-bottomed flask assembled with a condenser and a dropping funnel with methanol (260 mL). Sodium hydroxide (6.2 g, 0.155 mol) was added slowly with stirring and the addition process lasted for 3 hours and 30 minutes. Subsequently, the reaction mixture was heated to reflux condition to form a white suspension. Under reflux conditions, 2 M hydrochloric acid solution (121 mL) was added slowly and dropwise over a period of 1 h. The reaction solution gradually changed to yellow color. Upon completion of the reaction, the flask was transferred to an ice-water bath for cooling and the solid product precipitated at room temperature. The precipitate was collected by filtration and washed sequentially with a 2:1 methanol/water mixture (35 mL) and water (50 mL). The resulting solid product was dried overnight at room temperature to yield 19.68 g (75% yield) of the target compound. Nuclear magnetic resonance hydrogen spectroscopy (1H NMR, 300 MHz, DMSO-d6) data: δ 9.12 (m, 1H), 8.40 (dd, J = 2.1 Hz and 8.1 Hz, 1H), 8.12 (dd, J = 0.9 Hz and 8.4 Hz, 1H), 3.89 (s, 3H). Nuclear magnetic resonance carbon (13C NMR, 75.45 MHz, DMSO-d6) data: δ 165.9, 165.0, 152.1, 150.2, 138.8, 128.3, 125.0, 53.2.
