中国医药工业杂志2024,Vol.55Issue(8) :1089-1092.DOI:10.16522/j.cnki.cjph.2024.08.007

本芴醇的合成工艺改进

Improvement of the Synthesis Process of Benfluorenol

杨康 郑群 吴炜婷 陈旭香 赵建宏
中国医药工业杂志2024,Vol.55Issue(8) :1089-1092.DOI:10.16522/j.cnki.cjph.2024.08.007

本芴醇的合成工艺改进

Improvement of the Synthesis Process of Benfluorenol

杨康 1郑群 1吴炜婷 1陈旭香 1赵建宏1
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作者信息

  • 1. 华东理工大学药学院,制药工程与过程化学教育部工程研究中心,上海 200237
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摘要

以芴(2)为原料,经三氯异腈尿酸氯化得2,7-二氯芴(3),与氯乙酰氯发生酰化反应生成2,7-二氯芴-4-氯乙酮(4),再将还原、环合、胺化"一锅法"合成得到α-(二正丁胺甲基)-2,7-二氯-4-芴甲醇(5),最后与对氯苯甲醛缩合得到本芴醇(1),总收率36%,纯度99.4%.新工艺中的氯化采用三氯异腈尿酸为氯化剂,反应选择性与安全性提高;还原、环合与胺化运用"一锅法"完成,反应温度降低,反应周期缩短,生产效率提高(从60%提高到80%),适合放大生产.

Abstract

Using fluorene(2)as the starting material,it was chlorinated by trichloroisocyanuric acid to obtain 2,7-dichlorofluorene(3),which was acylated with chloroacetyl chloride to produce 2,7-dichlorofluorene-4-chloroethyl ketone(4).Then,α-(di-n-butylaminomethyl)-2,7-dichloro-4-fluorenylmethanol(5)was obtained via reduction,cyclization and amination by one-pot method.Finally,5 was condensed with p-chlorobenzaldehyde to obtain benfluorenol(1),with an overall yield of 36%and a purity of 99.4%.The improved process used trichloroisocyanuric acid as the chlorinating agent,which improved the selectivity and safety of the reaction.The reduction,cyclization and amination were completed by one-pot method,which reduced the reaction temperature,shortened the reaction cycle,improved production efficiency,and increased the yield from 60%to 80%.The improved process was simple to operate,low in production cost and suitable for industrial production.

关键词

本芴醇/工艺改进/抗疟药/合成

Key words

benfluorenol/process improvement/antimalarial drug/synthesis

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出版年

2024
中国医药工业杂志
上海医药工业研究院,中国化学制药工业协会

中国医药工业杂志

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影响因子:0.487
ISSN:1001-8255
参考文献量14
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