Synthesis
5-Methylpyrazine-2-carboxylic acid (300.84 g), AMBERLYST 15 ion-exchange resin (60.17 g) and ethanol (1004 g) were added to a 2L four-necked flask equipped with a mechanical stirrer, a water condenser (with a gas inlet), and a thermocouple under nitrogen atmosphere. The reaction mixture was stirred under reflux conditions for about 16 h. The reaction progress was confirmed by GC or GC/MS monitoring. Upon completion of the reaction, the resin was removed by pressurized filtration and the resin was washed with ethanol. The washings were combined into an ethanol solution of the ester. Subsequently, the solvent was removed by distillation under reduced pressure to afford 336.7 g (93% yield) of ethyl 5-methylpyrazine-2-carboxylate, which can be used directly in subsequent experiments. In addition, the product could be further purified by a thin film evaporator at 125 °C/3 mmHg, the product obtained by distillation was almost colorless and crystallized at about 20 °C.
References
[1] Patent: US2005/261312, 2005, A1. Location in patent: Page/Page column 2
[2] Patent: WO2003/76440, 2003, A1. Location in patent: Page/Page column 74-75
[3] Patent: US2005/239803, 2005, A1. Location in patent: Page/Page column 2
[4] Patent: US2005/261312, 2005, A1. Location in patent: Page/Page column 2
[5] Asian Journal of Chemistry, 2016, vol. 28, # 11, p. 2453 - 2456
