他米巴罗汀的合成工艺改进

Process improvement of tamibarotene preparation

目的改进他米巴罗汀的合成工艺。方法以2,5-二甲基-2,5-己二醇为起始原料经氯代后与乙酰苯胺进行Friedel-Crafts环合反应制得1,2,3,4-四氢-1,1,4,4-四甲基-6-乙酰氨基萘,再经脱乙酰基、酰化、水解共5步反应合成了抗白血病药物他米巴罗汀。结果优化后的工艺成本低、后处理容易、产物纯度高(纯度>99.7%,单个杂质<0.1%)、收率高。结论新工艺的总收率达到26.6%,且适合工业化生产。目标产物结构经1H-NMR,ESI-MS和元素分析确证。

Objective To improve the preparation process of tamibarotene. Methods 1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-aeetylaminonaphthalimide was prepared from 2,5-dimethyl-2,5-hexanediol by chloridized and Friedel-Craft reaction with acetanilide, which was subjected to deaeylation, aeylation and bydrolyzation to give tamibarotene. Results The process was successfully improved due to low cost, easier post-processing and good yield. The purity of the product was high （ 〉99.7% ） and no impurity more than 0.1% . Conclusion The total yield of the improved process was 26.6% , which was more suitable for industrial manufacturing. The structure of temibarotene was confirmed by I H-NMR, ESI-MS and elementary analysis.