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

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.