帕米膦酸二钠合成工艺改进

Ameliorating synthetic method of disodium pamidronate

目的合成-氨基-1-羟基-亚丙基-二膦酸二钠盐(帕米膦酸二钠)工艺改进。方法以β-丙氨酸为主要原料与三氯氧磷和亚磷酸反应的工艺为基础。(1)在反应体系中添加氯苯;(2)直接采用大量水洗纯化中间产品;(3)直接用氢氧化钠固体成钠盐。结果原文献收率29.7%,现提高到47.3%,工艺简化。结论经以上工艺改进产品收率大大提高,同时也改进了工艺。

Aim To improve the synthetic method of disodium pamidronate.Methods β-alanine was used to react with phosphorus oxychloride and phosphorous acid.First,chlorobenzene was added to the reaction;Second,a large quantity of water was adopted to wash the intermediate to get a pure pamidronic acid;Third,sodium hydroxide was solidified to get sodium salt.Result The yield was increased from 29.7% to 47.3%,and the craft was ameliorated.Conclusion The craft was ameliorated by the above method and the yied was greatly increased.