改进的锂卤交换法合成N-Boc-6-氨甲基烟醛  

Preparation of N-Boc-6-aminomethylnicotinaldehyde by modified lithium-halide exchange method

作　　者：程纯儒 魏锟 方大双 薛云杰 林琪宇 CHENG Chun-ru;WEI Kun;FANG Da-shuang;XUE Yun-jie;LIN Qi-yu(School of Chemical Engineering,Sichuan University of Science and Engineering,Zigong 643000,China;Zigong Inspection and Testing Institute,Zigong 643000,China)

机构地区：[1]四川轻化工大学化学工程学院,四川自贡643000 [2]自贡检验检测院,四川自贡643000

出　　处：《化学研究与应用》2021年第9期1829-1833,共5页Chemical Research and Application

基　　金：国家自然科学基金项目(81373964)资助;精细化工助剂及表面活性剂四川省高校重点实验项目(2019JXZ02)资助;绿色催化重点实验室项目(LZJ18202)资助;自贡科技局项目(2019YYJC32)资助。

摘　　要：含酰胺基团的芳卤化合物锂卤交换制备芳醛化合物往往会失败或收率极低,本文采用改进的锂卤交换法成功地合成了单胺氧化酶抑制剂的关键中间体N-Boc-6-氨甲基烟醛。以5-溴-2-氰基吡啶为原料,通过“一锅法”直接将氰基还原成氨基的同时接上Boc保护基,随后在正丁基锂和异丙基氯化镁的作用下发生金属卤素交换反应,再与DMF反应,最终成功合成目标化合物N-Boc-6-氨甲基烟醛,总收率为70.5%。产物经1H-NMR、13C-NMR分析确证为目标产物。与文献报道的路线相比,该合成路线大大缩短。Preparation of aryl aldehyde through aryl halide by lithium-halide exchange method will result in failure or extremely low yields.In present study,N-Boc-6-aminomethylnicotinaldehyde,a key intermediate of monoamine oxidase inhibitor,was synthesized by modified lithium-halide exchange method.The target compound was successfully synthesized by using 5-bromo-2-cyanopyridine as raw material through two reaction steps including“one-pot reaction”directly from cyano group to N-Boc-amino group,metal-halide exchange reaction.The total yield was up to 70.5%.The products were characterized by interpreting 1H-NMR and 13C-NMR spectra.Compared with the reported synthetic routes,the present route was much shorter.

关 键 词：N-Boc-6-胺甲基烟醛 药物中间体 锂卤交换 单胺氧化酶抑制剂 

分 类 号：O625.4[理学—有机化学]