内-9-甲基-9-氮杂二环[3.3.1]壬-3-烷胺的合成工艺改进

Process Improvement on the Synthesis of endo-9-Methyl-9-azabicyclononan-3-amine

以柠檬酸为起始原料,经氧化、Mannich反应、成肟、LiAlH4还原以及内外式产物分离,合成了制备盐酸格拉司琼的关键中间体内-9-甲基-9-氮杂二环[3.3制药技术.1]壬-3-烷胺,总收率16.8%。其结构经1H NMR,IR和MS表征。

The key intermediate of preparing Granisetron hydrochloride,endo-9-methyl-9-azabicyclononan-3-amine（endo-1）,was synthesized by oxidation of citric acid,then by the Mannich reaction,synthesis of Oxime,LiAlH4 reduction and the separation of endo-and exo-products in total yield over 16.8%.The structure was confirmed by IR,NMR and MS.