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:AzetidineAzetidine-3-ylmethanolPharmaceutical intermediatesSynthesis. 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

作者	单位	E-mail
杨阳		2416078192@qq.com
全宏冬	赤峰瑞阳化工有限公司
范东升	喀什大学化学与环境科学学院 新疆喀什
赵彦梁	喀什大学化学与环境科学学院 新疆喀什
赵佩佩	天津国际生物医药联合研究院
袁昊林	南开大学药学院
贺万丽	天津国际生物医药联合研究院
蔡岩	天津国际生物医药联合研究院	caiyan_86@163.com

摘要点击次数:198 全文下载次数:0 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. 查看全文查看/发表评论下载PDF阅读器 相关附件：附件1版权转让声明书附件1 -->