汇聚法合成高纯度阿托伐他汀钙的工艺研究  

Study on the Process of Synthesis of High-purity Atorvastatin Calcium by Convergent Method

作　　者：潘琳 易志恒 王珊 向圆圆 王福东[2] 彭东明[2] Pan Lin;Yi Zhiheng;Wang Shan;Xiang Yuanyuan;Wang Fudong;Peng Dongming(Hunan Dino Pharmaceutical Limited by Share Ltd.,Changsha 410005;School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南迪诺制药股份有限公司,湖南长沙410005 [2]湖南中医药大学药学院,湖南长沙410208

出　　处：《广东化工》2021年第23期31-33,共3页Guangdong Chemical Industry

基　　金：湖南省自然科学株洲联合基金资助项目(2019JJ60071);湖南省教育厅科学重点研究项目(18A211);湖南省教育厅科学研究项目(19C1417);药学一流学科开放基金(科函[2020]4号-2020YX01、2020YX07);湖南省科技计划项目(2014XK4007)。

摘　　要：采用汇聚法合成策略以ATS-9为起始原料与特戊酸成盐,然后以ATS-9特戊酸盐和M4为原料汇聚合成高纯度的中间体L1,再酸解、碱解、精制并对合成工艺条件进行了优化,制得高纯度的阿托伐他汀钙,总收率为77.73%,纯度达99.86%,其结构经1H NMR和MS确证。该合成工艺反应条件温和,转化率高,所用原料经济易得,大大降低了生产成本,适宜于大规模工业化生产。High-purity atorvastatin calcium can be obtained with a total yield of 77.73 % and a purity of 99.86 % by convergence synthesis strategy that ATS-9 was used as the starting material to form a salt with pivalic acid, and then ATS-9 pivalate and M4 were used as raw materials to converge to form a high-purity intermediate L1, which was then acid hydrolyzed, alkaline hydrolyzed and the synthesis process conditions were optimized. Its structure was confirmed by 1 H NMR and MS. Compared with the traditional process refined, the synthetic strategy had mild reaction conditions, high conversion rate, economical and easy-to-obtain raw materials, which greatly reduces production costs and was suitable for large-scale industrial production.

关 键 词：阿托伐他汀钙 合成 汇聚法 高纯度 工艺研究 

分 类 号：TQ460.6[化学工程—制药化工]