恩卡胺的合成

SYNTttESIS OF ENCAINIDE

2-甲基吡啶与碘甲烷反应生成碘化1,2-二甲基吡啶铭(3);后者与邻硝基苯甲醛反应得碘化1-甲基-2-(邻硝基苯乙烯基)吡啶鎓(4);然后经催化氢化生成1-甲基-2-[2-(邻氨基苯)乙基]哌啶(2);再与对甲氧基苯甲酰氯反应,形成恩卡胺盐基,四步总收率约40%。

α-Picoline reacted with methyl iodide to produce 1,2-dimethyl-pyridinium iodide(3),which was converted to 1-methyl-2-(o-nitrostyryl)pyridi-nium iodide(4)by condensation with o-nitrobenzaldehyde.Then 4 was subjected tocatalytic hydrogenation to give 1-methyl-2-(o-aminophenethyl)piperidine(2)which was transformed,into 1-methyl-2-[o-(p-methoxybenzamido)phenethyl]piperidine(1,encainide base)by reaction with p-methoxybenzoyl chloride.Thetotal yield was about 40%.