盐酸美金刚胺的合成工艺改进  

Improvement of synthetic process of memantine hydrochloride

作　　者：黄正义 田磊 程杰[2] 崔颖[2] 王辉[2] 

机构地区：[1]安徽贝克联合制药有限公司,安徽太和236604 [2]安徽省药物研究所,安徽合肥230022

出　　处：《安徽医药》2013年第1期24-25,共2页Anhui Medical and Pharmaceutical Journal

摘　　要：目的改进盐酸美金刚胺的合成工艺。方法以1,3-二甲基金刚烷为原料,在叔丁醇、乙腈、浓硫酸存在下,经Ritter反应生成1-乙酰胺基-3,5-二甲基金刚烷,再以聚乙二醇为溶剂,加入氢氧化钠水解得到美金刚胺,然后在异丙醇溶剂中盐酸化得到盐酸美金刚胺。总收率:70%。结果合成了具有良好化学纯度的盐酸美金刚胺(纯度99.9%,总收率70%)。结论改进的工艺明显提高了反应收率,工艺条件温和,合成步骤简洁,适合工业化生产。Objective To study the synthesis of memantine hydrochloride by improving its method.Methods Memantine hydrochloride was synthesized from 1,3-dimethyl-adamantane by using tert-butyl alcohol,acetonitrile,and sulphuric acid under Ritter conditions to give 1-acetamido-3,5-dimethyl-adamantane,which was hydrolyzed using NaOH with polyethylene glycol as solvent to give free base,then converted into its hydrochloride with isopropanol as solvent.The overall yield was 70%.Results Memantine hydrochloride was synthesized with high chemical purity（purity 99.9%;overall yield 70%）.Conclusion The improved technique significantly increaces the reaction yield.It has mild reaction condition and simple synthesized procedure,which is suitable for mass production.

关 键 词：盐酸美金刚胺 合成工艺改进 工业化生产 聚乙二醇 氢氧化钠 工艺条件 金刚烷 叔丁醇 

分 类 号：R914.5[医药卫生—药物化学]