磷酸氟达拉滨的制备  

Preparation of Fludarabine Phosphate

作　　者：郝二军 赵琰 贾茹萍 宋禹漫 崔杨波 李桐 卢丙辉 HAO Erjun;ZHAO Yan;JIA Ruping;SONG Yuman;CUI Yangbo;LI Tong;LU Binghui(Key Lab.of Green Chemical Media and Reactions,Ministry of Education,Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals,School of Chemistry and Chemical Engineering,Henan Normal University,Xinxiang 453007)

机构地区：[1]河南师范大学化学化工学院,精细化学品绿色制造河南省协同创新中心,绿色化学介质与反应教育部重点实验室,河南新乡453007

出　　处：《中国医药工业杂志》2024年第8期1098-1099,共2页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金项目(21602045);河南省高等学校重点科研项目计划(21A150002);河南师范大学研究生科研创新项目(YL202110)。

摘　　要：以氟达拉滨为原料,与磷酸三乙酯和三氯氧磷反应制得磷酸氟达拉滨,所得产品收率约81%,纯度99.91%。该工艺反应条件温和、操作简便且工艺稳定,已完成工艺验证,适合工业化生产。An improved synthetic process of fludarabine phosphate(1)was developed.Commercially available fludarabine was subjected to a nucleophilic substitution with triethyl phosphate.Subsequently,the target compound 1 was obtained through hydrolysis of triethyl phosphate on exposure to phosphorus oxychloride condition with an overall yield of 81%and a purity of 99.91%.The optimized process bearing mild reaction conditions,simple operation and stable process had been tested by process verification,and was suitable for industrial production.

关 键 词：磷酸氟达拉滨 磷酸三乙酯 三氯氧磷 合成 

分 类 号：TQ460.6[化学工程—制药化工] R927.2[医药卫生—药学]