氮杂环丁烷类药物中间体的合成

以1-叔丁氧羰基-3-羟基氮杂环丁烷为原料,叠氮化钠和邻苯二甲酰亚胺钾盐为氨源,考察了两种途径合成1-叔丁氧羰基-3-氨基氮杂环丁烷这种药物中间体实验的可操作性、安全性能、产率高低和后处理的繁简。实验表明,当用叠氮化钠为氨源取代羟基成叠氮基时,经过分批加入锌粉可还原成伯氨,得到70%的产率。但是叠氮化钠毒性较强,受热或震动摩擦可发生爆炸,操作难度较大。当用邻苯二甲酰亚胺钾盐为氨源,生成的叔氨在乙醇水合肼溶液中加热回流肼解生成伯氨,产率为63%。产率虽然低于前一种方法,但是实验的可操作性很强,安全且后处理简单。

Synthesis of azetidine medicinal intermediate

Two ways in synthesis of pharmaceutical intermediate 1-(tert-butyl)-3-amioazetidine were investigated by 1-(tert-butyl)-3-hydroxyazetidine as raw materials,sodium azide and phthalimide potassium salt as the ammonia source,and experiments operability,security,yield and post-processing level of them were studied.Experiments showed that when using azide as the ammonia source to replace the hydroxyl into azido,then adding zinc powder can be reduced to the product,obtained 70% yield.However,sodium azide may be toxic,the operation is more difficult due to its explosion when heat or vibration.When potassium phthalimide was used as the ammonia source,the product was obtained by hydrazinolysis the tert-ammonia solution in hydrazine hydrate.The yield was 63%,though lower than the fomer method,but the experiment could be operational very strong,safe and simple post-processing.