阿昔莫司的合成工艺改进

Improved Synthetic Method of Acipimox

以5-甲基吡嗪-2-羧酸(2)为原料,过氧化氢/钨酸钠为氧化剂,通过氢氧化钠调至pH 3~5以增大2在溶剂中的溶解度,解决了产物包裹原料的问题,反应彻底。活性炭趁热过滤步骤前移后,用丙酮和水的混合溶液打浆纯化即可得到纯度99.93%(其中2的含量不超过0.03%,过氧化物杂质不超过0.01%)的阿昔莫司,总收率约84%。优化后的工艺操作简单,易于工业化生产。

5-Methylpyrazine-2-carboxylic acid(2) was oxidated with hydrogen peroxide/sodium tungstate to produce acipimox.In the process,the pH value was adjusted to 3-5 with sodium hydroxide to increase the solubility of compound 2,so that the reaction was complete.After the filtration in heating with activated carbon,followed by the reslurry with the mixed solution of acetone and water,the target compound with purity of 99.93%(with no more than 0.03% of 2,and no more than 0.01% of the peroxide impurity) was obtained,and the total yield was about 84%.The improved process with simple operations was suitable for industrial application.