β-芳基-δ-氨基酸衍生物的新合成方法

A new synthesis of β-aryl-substituted-δ-amino acids derivatives

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-戊烯酸甲酯和芳基硼酸为原料，通过（1，5-环辛二烯）氯化铑（I）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 （Ⅲ）。利用1HNMR、13CNMR 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]2 0.005 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，实现盐酸高巴氯芬的快速制备。

Abstract:

For efficiently constructing functionalized β-aryl-δ-amino acid derivatives, starting from easily prepared 5-phthalimide-2-pentenoic acid methyl ester and arylboric acids as raw materials, nine kinds of 5-phthalimide-3-arylvalerate methyl ester were obtained via a [Rh(COD)Cl]2 catalyzed Michael reaction. And the yields were more than 95%. The obtained compounds were confirmed by 1HNMR, 13CNMR and HR-MS, respectively. Moreover, the optimum reaction conditions for synthesis of 5-phthalimide-3-arylvalerate methyl ester were as follows: methyl 5-phthalimide-2-pentenoate (0.2 mmol), arylboric acid (0.4 mmol), potassium hydroxide aqueous solution (0.1 mL, 1.0 mol/L), [Rh(COD)Cl]2 (0.005 mmol), 1,4-dioxane (1.0 ml) as solvent，reaction time of 10 hours，at the temperature 100℃. In addition, 5-phthalimide-3-p-chlorophenylvalerate methyl ester can be used for the rapid preparation of the active molecules of homobaclofen hydrochloride.