Abstract: The property and pharmacological actions of atorvastatin calcium were introduced briefly. The synthesis route of atorvastatin calcium was analyzed. The (4R-Cis)-6-{2-[2-(4-Fluoro phenyl)]-5-(isopro)-3-phenyl-4-[(phenylaminocarbonyl-1H-pyrrol-1-yl)ethyl]-2,2-dimethyl-1,3dioxan-4-tert-butyl acetate was selected as the raw material for the acidification and neutralization of Atorvastatin Calcium, and corresponding synthetic process was optimized. The total yield was 91.29% on the condition of 2 mol/L hydrochloric acid, 1∶2.2 molar ratio of material and hydrochloric acid, reaction time 75 min. Crude product was re-crystallized with n-hexane and dichloromethane, and formless atorvastatin Calcium was obtained. The structure characterization confirmed that the product was atorvastatin calcium.

Key words: atorvastatin calcium, synthesis, critical technology, optimization

摘要： 简要介绍了阿托伐他汀钙的性质和药理作用，分析了阿托伐他汀钙的全合成路线，选择以(4R-cis)-6-[2-(2-(4-氟基苯)-5-(1-异丙基)-3-苯基-4-[(苯胺)羰基-1H-吡咯-1-基)乙基]-2,2-二甲基-1,3-二氧己环-4-乙酸叔丁酯(Ⅱ)为原料经酸解、中和得到阿托伐他汀钙(Ⅰ)，并对其合成工艺进行了优化。合成过程中使用2 mol/L的盐酸，控制原料和盐酸的摩尔比在1∶2.2时，反应75 min得产物，产率高达91.29%；粗品选择二氯甲烷与正己烷为溶剂进行重结晶可以得到较好的无定形阿托伐他汀钙固体；产品经结构分析确认为阿托伐他汀钙。

关键词: 阿托伐他汀钙, 合成, 关键工艺, 优化