β-芳基-δ-氨基酸衍生物的新合成方法  

A new synthesis method of β-aryl-δ-amino acid derivatives

作　　者：张向阳[1] 王菲菲 唐裕才 申有名[1] 陈骏 ZHANG Xiangyang;WANG Feifei;TANG Yucai;SHEN Youming;CHEN Jun(Changde Engineering Technology Research Center of Key Preparation Technology of Biomedical Polymer Materials,Hunan University of Arts and Science,Changde 415000,Hunan,China;Chongqing Key Laboratory of Industrial Fermentation Microorganism,Chongqing University of Science&Technology,Chongqing 401331,China)

机构地区：[1]湖南文理学院生物医药高分子材料关键技术常德市工程技术研究中心,湖南常德415000 [2]重庆科技学院工业发酵微生物重庆市重点实验室,重庆401331

出　　处：《精细化工》2023年第1期139-145,共7页Fine Chemicals

基　　金：湖南省自然科学基金项目(2020JJ4445,2020JJ5390);湖南省教育厅优秀青年项目资助(19B390)。

摘　　要：为高效构建β-芳基-δ-氨基酸衍生物,以易制备的5-邻苯二甲酰亚胺基-2-戊烯酸甲酯和不同芳基硼酸为原料,通过(1,5-环辛二烯)氯化铑二聚体[[Rh(COD)Cl]_(2)]催化的Michael加成反应,以95%以上的产率获得了9种5-邻苯二甲酰亚胺基-3-芳基戊酸甲酯(Ⅲa~i)。利用^(1)HNMR、^(13)CNMR和HRMS对合成产物的结构进行了确证。合成5-邻苯二甲酰亚胺基-3-芳基戊酸甲酯最佳的反应条件为:5-邻苯二甲酰亚胺基-2-戊烯酸甲酯0.2 mmol,芳基硼酸0.4 mmol,KOH水溶液(0.1 mL,1.0 mol/L),[Rh(COD)Cl]20.005 mmol,溶剂为1.0 mL 1,4-二氧六环,反应温度100℃,反应时间10 h。此外,以5-邻苯二甲酰亚胺基-3-对氯苯基戊酸甲酯(Ⅲb)为原料,实现了盐酸高巴氯芬的快速制备。For efficient construction of functionalized β-aryl-δ-amino acid derivatives,nine kinds of 5-phthalimide-3-arylvalerate methyl esters(Ⅲa~i),with yields of more than 95%,were synthesized via(1,5-cyclooctadiene)rhodium chloride dimer{[Rh(COD)Cl]_(2)}catalyzed Michael reaction of easily prepared 5-phthalimide-2-pentenoic acid methyl ester and different arylboronic acids,and then characterized by ^(1)HNMR,^(13)CNMR and HRMS for structural confirmation.Moreover,the optimum reaction conditions for synthesis of 5-phthalimide-3-arylvalerate methyl ester were found to be as follows:5-phthalimide-2-pentenoic acid methyl ester 0.2 mmol,arylboric acid 0.4 mmol,potassium hydroxide aqueous solution 0.1 mL(1.0 mol/L),[Rh(COD)Cl]20.005 mmol,1,4-dioxane as solvent 1.0 mL,reaction time 10 h,and reaction temperature 100℃.In addition,5-phthalimide-3-p-chlorophenylvalerate methyl ester obtained could be used for the rapid preparation of homobaclofen hydrochloride.

关 键 词：δ-氨基酸衍生物 高效转化 新策略 铑催化 医药原料 

分 类 号：O629.71[理学—有机化学]