恩他卡朋的合成改进

Improvements on the Synthesis of Entacapone

以3,4-二羟基-5-硝基苯甲醛(3)和N,N-二乙基氰乙酰胺(5)为中间体,在哌啶和Ando催化剂的异丙醇体系中经knoevenagal反应合成得到了恩他卡朋(6)。中间体3的制备由香兰素经常温硝化、脱甲基制得。中间体5的制备由氰基乙酸在二环己基碳二亚胺(DCC)作用下经酰胺化一步制得,条件温和,收率较高,避免使用剧毒的氰化钠。总收率从文献的30%提高到67%。合成的恩他卡朋结构经核磁与质谱分析确证。

Entacapone was synthesized via Knoevenagal reaction of N,N-diethyl-2-nitrilo-acetamide （5） with 3,4-dihydroxy-5-nitro-benzaldehyde （3） in solvent of isopropanol containing piperidine and ando-eatalyst. 3 was obtained from vanillin by nitration and demethylation. 5 was synthesized from cyanoacetic acid and diethylamine via DCC coupling under mild conditions. The overall yield was improved from 30% to 67%. The structure of entacapone was confirmed by ^1H NMR and MS.