3-羟甲基氮杂环丁烷盐酸盐的实用合成方法

氮杂环丁烷类化合物是一类重要的饱和四元含氮杂环化合物,在药物研发中有着广泛的应用。本文以二苯甲胺和环氧氯丙烷为起始原料,在碱性条件下反应关环构建N-杂环丁烷母核,之后依次发生羟基的氧化、Wittig反应生成环外双键,随后采用硼氢化氧化反应将双键转化为羟甲基,最后氢化脱去二苯甲基得到目标产物3-羟甲基氮杂环丁烷,反应的5步转化总收率为40%。该合成方法操作简单,原料廉价易得,避免了剧毒试剂的使用,具有很好的工业化前景。

A Practical Synthetic Method of Azetidin-3-ylmethanol Hydrochloride

Azetidine is a kind of very important and versatile compounds. They are wildly used in new drug development. In this article, we reported a new synthetic method of azetidine-3-ylmethanol hydrochloride which is the key material in azetidine chemistry, however, the synthesis of azetidine-3-ylmethanol is complex and the cost of it is still expensive. We used benzhydrylamine and epoxy chloropropane as starting materials, they initially underwent ring closing reaction under the basic condition to form the four member ring, oxidation of hydroxyl group and Wittig reaction then occurred to form the terminal olefin, borohydride oxidation reaction was then taken place to transform the terminal olefin to hydroxyl group, finally removed the protect group of amine to produce the target compound. The total yield of this new synthetic method is 40% for 5 steps, and the synthesis operation in the whole process is simple. All reagents in the synthesis procedure are commercially available and the use of toxic reagents is avoided. This novel synthesis method of azetidine-3-ylmethanol is very promising in further large scale production.