GENERAL STEPS: 2-Pyridinecarboxylic acid (5.0 g, 40.6 mmol) was dissolved in SOCl2 (15 mL) cooled to 0 °C, H2O (950 μL) was added slowly, followed by refluxing the reaction mixture for 1 hour. After the reaction mixture was cooled to room temperature, SOCl2 (15 mL) was added additionally and the reaction was continued to reflux for 2 days. After cooling to room temperature again, a third batch of SOCl2 (15 mL) was added and the mixture was continued to reflux for 2 days. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure and the resulting residue was dissolved in MeOH (30 mL) and refluxed overnight. Subsequently, a solution of NaOMe (4.4 g, 81.2 mmol) in MeOH (50 mL) was added to the reaction system and the reaction was continued at reflux for 2 days. At the end of the reaction, the solvent was removed by distillation under reduced pressure and the residue was dissolved in water and extracted with CHCl3. The organic phases were combined, dried with MgSO4 and concentrated under reduced pressure. The crude product was purified by SiO2 fast column chromatography with the eluent ratio of hexane:AcOEt = 1:1→1:4→1:10 to obtain the target product. Finally, the resulting solid was washed with hexane-Et2O (1:1) to afford methyl 4-methoxypyridine-2-carboxylate (1.8 g, 26% yield) as a light yellow solid.
