1-叔丁氧羰基-(S)-2-羟甲基氮杂环丁烷的合成  

Synthesis of 1-Boc-(S)-2-(hydroxymethyl)azetidine

作　　者：胡涛 朱晓鹤 朱云龙 HU Tao;ZHU Xiao-he;ZHU Yun-long(Yangtze River Drag Research Institue,State Key Lab of Advanced Pharmaceutical Formulation with High Technology,Taizhou 225321,China)

机构地区：[1]扬子江药物研究院,药物制剂新技术国家重点实验室,江苏泰州225321

出　　处：《精细化工中间体》2020年第2期30-33,共4页Fine Chemical Intermediates

摘　　要：报道了一种合成(S)-2-羟甲基氮杂环丁烷的新方法,即以γ-丁内酯为起始原料,经溴代开环成2,4-二溴丁酸甲酯(2),然后与(S)-α-苯乙胺双取代环化生成氮杂1-[(S)-1-苯乙基]-2-甲氧羰基氮杂环丁烷的两种非对映异构体3a(2S,1′S)和3b(2R,1′S),经柱层析分离,氢化铝锂还原成醇(4)后,氢解脱去(S)-1-苯乙基和引入Boc保护基生成标题化合物1-叔丁氧羰基-(S)-2-羟甲基氮杂环丁烷。总共4步反应,总收率为40%。1H NMR和MS表征确证了关键中间体和目标产物结构。A novel synthetic approach of(S)-2-(hydroxymethyl)azetidine was described.Starting fromγ-butyrolactone,the ring-opening bromization gave methyl 2,4-dibromobutanoate 2.The subsequent bissubstitution cyclization with(S)-α-phenylethanamine provided diastereoisomers 3a and 3b of(S)-methyl 1-((S)-1-phenylethyl)azetidine-2-carboxylate,which could be easily isolated by the column chromatography.The reduction into alcohol 4 with lithium aluminum hydride,followed by the hydrogenesis and Boc protection afforded the title compound(S)-tert-butyl 2-(hydroxymethyl)azetidine-1-carboxylate with an overall yields of 40%.The related compounds were confirmed by 1H NMR and MS.

关 键 词：Γ-丁内酯 (S)-α-苯乙胺 非对映异构体 2(S)-羟甲基氮杂环丁烷 

分 类 号：TQ463[化学工程—制药化工]