左旋盐酸去甲基苯环壬酯的合成新方法

摘要

目的 合成新型M4受体选择性拮抗剂左旋盐酸去甲基苯环壬酯.方法 以苄胺为原料制备N,N-二乙氧基甲基苄胺,该苄胺与环己酮反应、选择性还原,再与(R)-α-苯基-α-环戊基-α-羟基乙酸甲酯反应,经氢化、成盐得到目标产物左旋盐酸去甲基苯环壬酯,总收率为8.0%.结果与结论 目标化合物的结构经元素分析、核磁共振氢谱、质谱确证.新方法操作简便,以新旧合成路线中共有贵重原料?-α-苯基-α-环戊基-α-羟基乙酸甲酯计算,产品收率较原方法提高了10.6%,降低了成本,且利于环保.%Levodesmethylphencynonate hydrochloride (1), a novel selective M4 muscarine receptor antagonist, has been chosen as a candidate of anti-Parkinson's disease drug characterized by its good efficiency, high selectivity and low toxicity. A new synthetic method in the search for more economical and environmental friendly process was developed. The starting compound Af,N-diethoxylmethy benzyl amine was prepared by benzyl amine and ethanol, then via Mannich reaction with cyclohexanone, afterwards selective hy-drogenation and ester exchange with (R)-methyl-a-phenyl-a-cyclopentyl-a-hydroxy acid ester, hydrogena-tion,saltization to obtain target compound(l). The overall yield was 8.0% ,which increased 10.6% based on common chiral raw material ( R) -methyl-a-phenyl-a-cyclopentyl-a-hydroxy acid ester. The chemical structure of levodesmethylphencynonate hydrochloride was characterized by MS,' H-NMR and element analysis. Compared with the original synthetic process, the new route is facile and suitable for industrialized production with lower cost,lower pollution and higher yield.