双膦酸类药物帕米膦酸钠合成工艺的研究_范文明.pdfVIP

第38 卷第1 期 V ol. 38 N o. 1 20 10 年2 月 JO U RN A L OF ZHEJ IA N G U N IV ERSIT Y OF T E CH N OL O GY F eb. 2010 , , , , , 310032) : 研究了溶剂法和熔融法以B- 丙氨酸与亚膦酸反应, 然后加盐酸进行水解, 到帕米膦酸, 再与 氢氧化钠发生中和反应生成帕米膦酸二钠的工艺. 并对熔融法合成帕米膦酸二钠的反应中有可能 影响产品收率的各种因素, 特别是投料配比的选择反应时间水解时间等因素进行了工艺优化. 最 终在最佳的工艺参数下合成帕米膦酸二钠的总收率为36 . 47% . 该工艺具有毒性小的优点, 并且提 高了帕米膦酸二钠的收率. 通过IR , 1 H N M R 及M S 测试手段分析, 证实产品结构正确. : 双膦酸盐; 帕米膦酸钠; 合成工艺; 影响因素 : O623 . 627 : A : 1006-4 303 2010) 01- 0019- 04 Study on synthetic method of bone resorption inhibitor pamidronate disodium FA N Wen- ming , DON G H ua- qing , LIU Zong-w ei, L I Y u-jin, GA O J ian- ro ng St at e K ey Laborat ory Breeding Bas e of Green C hemi st ry- S ynt hes is T echology , Zh ejiang U niversit y of T echnol ogy , H angzhou 310032, C hina) Abstract: P am idronate sodium w as pr epar ed in the solvent stat e or in t he m olt en st at e by the reactio n bet ween B- alanine and pho sphor ou s acid, fo llow ed by hydr olysis t o get pamidr onat e acid w hich finally reacts w ith sodium hy drox ide t o o bt ain pamidro nat e sodium. T he opt im al pr ocess condit ions for synt hesizing pamidr onat e so dium in melt en stat e w ere invest igat ed in t his paper, w hich included t he f eed r at io, r eact ion t ime, hy dro lysis t im e and et c. T he y ield of pamidronat e sodium w as 36. 47% under t he opt imal condit io ns . T his pro cess show s som e advant ages like low er t ox icit y and higher yield. T he st ruct ure of product w as examined by u sing IR, MS, N M R.