| 杨阳,全宏冬,范东升,赵彦梁,赵佩佩,袁昊林,贺万丽,蔡岩.化学通报,2021,84(8):841-846. |
| 3-羟甲基氮杂环丁烷盐酸盐的实用合成方法 |
| A Practical Synthetic Method of Azetidin-3-ylmethanol Hydrochloride |
| 投稿时间：2021-01-07 修订日期：2021-03-03 |
| DOI： |
| 中文关键词: 氮杂环丁烷 3-羟甲基氮杂环丁烷 药物中间体 合成 |
| 英文关键词:Azetidine Azetidine-3-ylmethanol Pharmaceutical intermediates Synthesis. |
| 基金项目:南开大学沧州渤海新区绿色化工研究院基金项目(NCC2020FH01)资助 |
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| 中文摘要: |
| 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。本文报道了一种3-羟甲基氮杂环丁烷盐酸盐的新合成方法，该化合物是很多氮杂环丁烷衍生物合成的关键原料，它目前的合成工艺较为复杂而导致其售价昂贵。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。 |
| 英文摘要: |
| 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. |
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