Ethyl 4-hydroxy-5-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate (5.0 g, 21.4 mmol) was used as the raw material, which was dissolved in phosphoric acid trichloride (100 mL), and the reaction was carried out by refluxing for 12 hours at 125 °C. The reaction process was monitored by LCMS. Upon completion of the reaction, most of the phosphoric acid trichloride was removed by evaporation and the residue was slowly added dropwise to ice water (100 mL). Subsequently, the reaction mixture was neutralized with aqueous sodium carbonate (50 mL) and extracted with ethyl acetate (200 mL). The organic layer was separated and the organic phases were combined, washed sequentially with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Finally, the residue was purified by silica gel column chromatography (eluent ratio of petroleum ether:ethyl acetate=15:1) to afford the target product ethyl 4,6-dichloro-5-methylnicotinate (1.6 g, 32% yield) as a yellow oil. The result of mass spectrometry (ES+) analysis: the theoretical value of C9H9Cl2NO2 was 232,234 and the measured value was 233,235 [M+H].
