琥珀酸 S-美托洛尔的合成工艺及其杂质控制研究
Synthesis technique and control of impurities of (S)-Succinate Metoprolol
狄潘潘 1李家明 1徐自奥 2刘海亮 2李晓祥2
作者信息
- 1. 安徽中医药大学药学院，安徽 合肥 230038
- 2. 安徽省新星药物开发有限责任公司，安徽 合肥 230088
- 折叠
摘要
目的：通过工艺优化，合成高光学纯度（≥99．7％）的琥珀酸 S-美托洛尔及其关键杂质。方法以对甲氧基乙基苯酚， R-表氯醇和异丙胺为起始原料，通过反应条件的摸索与优化，并经纯化、拆分后，制备出纯度大于99．5％的 S-美托洛尔，同时合成其中2个关键杂质。结果所制备的高光学纯度的琥珀酸 S-美托洛尔及相关杂质，经核磁共振氢谱（NMR），质谱（MS），高效液相色谱（HPLC）确证。结论优化后的工艺收率高，易操作，适合工业化生产。
Abstract
Objective To optimize the synthetic method for synthesizing high optical purity (≥99.7%)S-succinate metoprolol and two key impurities.Methods With p-(2-methoxyethyl)phenol,R-epichlorohydrin and isopropylamine as starting materials,the prepa-ration of high purity (>99.5%)of S-metoprolol was made after purification and separation.Results S-metoprolol and the related im-purties were confirmed by proton magnetic resonance spectroscopy(NMR),mass spectrum (MS)and high performance liquid chroma-tography (HPLC).Conclusions The yield of optimized process is high,which is easy to operate and suitable for industrial production.
关键词
S-美托洛尔/合成/杂质/工艺优化Key words
S-metoprolol/synthesis/impurity/process optimization引用本文复制引用
出版年
2015
NETL
NSTL
万方数据