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| 高效双膦酸药物唑来膦酸合成工艺改进 | |
| 引用本文： | 杨清翠,孙晓红,刘源发,马海霞,陆文婷,靳如意. 高效双膦酸药物唑来膦酸合成工艺改进[J]. 化学工程, 2012, 40(4): 45-48 |
| 作者姓名： | 杨清翠 孙晓红 刘源发 马海霞 陆文婷 靳如意 |
| 作者单位： | 1. 西北大学化工学院,陕西西安710069;西安建筑科技大学理学院,陕西西安710055 2. 西北大学化工学院,陕西西安710069;西北大学化学研究所,陕西西安710069 3. 西北大学化学研究所,陕西西安,710069 4. 西北大学化工学院,陕西西安,710069 |
| 基金项目： | 国家自然科学基金资助项目(21073141);西北大学研究生创新基金资助项目(10YZZ32);陕西省自然科学基金资助项目(2011JM2114) |
| 摘 要： | 对以咪唑和氯乙酸乙酯为原料,经N-烷基化反应、成盐得咪唑乙酸盐酸盐,再与三氯氧磷和磷酸反应后水解合成唑来膦酸的工艺进行了研究。重点探讨了反应溶剂对合成唑来膦酸工艺的影响。结果表明:采用甲苯、体积分数95%乙醇、质量分数85%磷酸为反应溶剂,不仅毒性和成本低,反应过程和前后处理的操作更加合理和简便,总收率43%。对以甲苯为溶剂的N-烷基化反应条件进行了优选,优化结果为反应温度65—70℃,反应时间4.5—5.0 h。得到操作简便、合成周期短、成本低、收率较高,易实现工业化的唑来膦酸合成工艺。 |
| 关 键 词： | 唑来膦酸 溶剂 N-烷基化 工艺优化 |
Improved process of highly potent bisphosphonate zoledronic acid |
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| YANG Qing-cui , SUN Xiao-hong , LIU Yuan-fa , MA Hai-xia , LU Wen-ting , JIN Ru-yi. Improved process of highly potent bisphosphonate zoledronic acid[J]. Chemical Engineering, 2012, 40(4): 45-48 | |
| Authors: | YANG Qing-cui SUN Xiao-hong LIU Yuan-fa MA Hai-xia LU Wen-ting JIN Ru-yi |
| Affiliation: | 1 (1.School of Chemical Engineering,Northwest University,Xi′an 710069,Shaanxi Province,China;2.School of Science,Xi′an University of Architecture and Technology,Xi′an 710055,Shaanxi Province,China;3.Chemical Research Institute,Northwest University,Xi′an 710069,Shaanxi Province,China) |
| Abstract: | An improved process for preparing bisphosphonate zoledronic acid was studied.The intermediate product 1H-imidazol-1-yl-acetic acid hydrochloride was synthesized with imidazole and ethyl chloroacetate as raw materials via N-alkylation and salification.Then final product zoledronic acid was prepared with 1H-imidazol-1-yl-acetic acid hydrochloride,phosphorus oxychloride and phosphoric acid by hydrolysis.The influence of the solvents on the reaction was mainly discussed.The results show that the toluene,ethanol with volume fraction of 95%,phosphoric acid with mass fraction of 85% are suitable for the zoledronic acid synthesis because of their lower poisonousness,low cost and easy operation as solvents.The overall yield of zoledronic acid is 43%.The optimized conditions for N-alkylation with the toluene as solvent are at 65-70 ℃ for 4.5-5.0 h.The novel process presents simple operation,short reaction time,low cost and is easy for industrial production of bisphosphonate zoledronic acid. |
| Keywords: | bisphosphonate zoledronic acid solvent N-alkylation process optimization |
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