一种盐酸非索非那定潜在杂质的合成
Synthesis of a Potential Impurity of Fexofenadine Hydrochloride
丁志新 1王震 1李成利 1李成斌 1付国兵 1张国荣1
作者信息
- 1. 西安万隆制药股份有限公司,陕西西安 710119
- 折叠
摘要
以2-[4-(4-氯-1-丁酰基)苯基]-2-甲基丙酸甲酯(2)为起始原料,在碳酸氢钠弱碱条件下关环得4-环丙基羰基-α,α-二甲基苯乙酸甲酯(3),经硼氢化钠还原得2-[4-(环丙基(羟基)甲基)苯基]-2-甲基丙酸甲酯(4),4在氢氧化钠溶液中水解得盐酸非索非那定潜在杂质2-[4-(环丙基(羟基)甲基)苯基]-2-甲基丙酸(1).3步反应总收率53.3％(以2计),纯度99.4％(HPLC),其结构经1H NMR和HRMS表征确认.该方法操作简单、安全.制备了 3个杂质对照品,为盐酸非索非那的质量控制提供了物质基础.
Abstract
A potential impurity of fexofenadine hydrochloride of 4-cyclopropylcarbonyl-α,α-dimethylbenzene acetic acid methyl ester(3)was synthesized from methyl 2-[4-(4-chlorobutanoyl)phenyl]-2-methylpropanoate(2)by cyclization under the weak alkaline condition,followed by a reduction reaction using sodium borohydride to give 2-[4-(cyclopropyl(hydroxy)methyl)phenyl]-methyl-2-methylpropionate(4).Finally,2-[4-(cyclopropyl(hydroxy)methyl)phenyl]-methyl-2-methylpropionic acid(1)was prepared through hydrolysis reaction using alkali methanol solution and salification with acid.The overall yield was 53.3％and the HPLC purity was 99.4％,and the stucture was confirmed.The process is easy and safe to operate.Three impurities of the intermediate and title product was synthesized.
关键词
盐酸非索非那定/有关物质/合成Key words
fexofenadine hydrochloride/related substances/synthesis引用本文复制引用
出版年
2024
NETL
NSTL
维普
万方数据