磷酸氟达拉滨的制备

Preparation of Fludarabine Phosphate

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.