右旋雷贝拉唑钠的制备工艺改进  

Improved process of dexrabeprazole sodium

作　　者：张春来[1] 罗宏军 姜琦 李国贤[1] 顾国庆 张杰[1] ZHANG Chunlai 1,LUO Hongjun 1 ,JIANG Qi 1,LI Guoxian 1,GU Guoqing 2,ZHANG Jie 1(1 Yangtze River Pharmaceutical Group Co.,Ltd.,Taizhou 225321;2 Jiangsu HaiCi Biological Pharmaceutical Co.,Ltd.,Taizhou 225321,Chin)

机构地区：[1]扬子江药业集团有限公司,泰州225321 [2]江苏海慈生物药业有限公司,泰州225321

出　　处：《中国药科大学学报》2018年第3期291-294,共4页Journal of China Pharmaceutical University

摘　　要：为改进右旋雷贝拉唑钠的制备工艺,简化合成步骤,提高产品质量和收率,获得稳定可行的生产工艺,以2-[[[4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基]硫代]-1H-苯并咪唑为起始原料,以钛酸四异丙酯和L-酒石酸二乙酯为手性催化剂,以过氧化氢异丙苯为氧化剂对其进行不对称氧化得到右旋雷贝拉唑,精制后与氢氧化钠成盐得目标化合物,收率为79%,产品HPLC纯度99.6%以上。目标化合物经NMR、IR、元素分析、LC-MS确证其结构。改进后的工艺生产周期短,操作步骤简单,产品收率和纯度得到提高,适合工业化生产。The aim of the work is to improve the synthetic process of dexrabeprazole sodium,enhance quality and yield of the product,simplify synthetic steps,and offer a stable and feasible process.Starting from 2-[[[4-（3- methoxypropoxy ）-3-methylpyridine-2-yl]methyl] thio]-1 H -benzimidazole,dexrabeprazole was produced by asymmetric oxidation reaction with oxidant cumene hydroperoxide in the presence of chiral catalyst tetraisopropyl titanate and L-（＋）-tartaric acid diethyl ester.Dexrabeprazole sodium was obtained by the reaction of purified dexrabeprazole with sodium hydroxide in a total yield of 79% with an HPLC purity of 〉99.5%.The structure of dexrabeprazole sodium was confirmed by NMR,IR,elemental analysis and LC-MS.The improved process of dexrabeprazole sodium possesses simple operations,good yield and high purity,which is feasible for industrialization.

关 键 词：右旋雷贝拉唑 不对称氧化 合成工艺 

分 类 号：R914[医药卫生—药物化学]