【摘要】 以3-奎宁酮和吩噻嗪为起始原料,经缩合制得美喹他嗪的关键中间体10-(3-羟基-1-氮杂双环[2,2,2]辛-3-基甲基)-吩噻嗪(4),4再经氯代、消除、Pd-C还原制得美喹他嗪。目标化合物的结构经红外、核磁共振氢谱及碳谱确证,总收率为41.9%。该工艺操作简便,适用于工业化生产。更多还原

【Abstract】 10-(3-Hydroxy-1-azabicyclo[2,2,2]oct-3-yl-methyl)-phenothiazine(4),a key intermediate of mequitazine,was obtained via condensation reaction from 3-quinuclidone with phenothiazine.4 was subjected to chlorination with phosphorus oxychloride to afford 10-(3-chloro-1-azabicyclo[2,2,2]oct-3-yl-methyl)-phenothiazine(5).5 was subsequently converted to(E)-10-(1-azabicyclo[2,2,2]oct-3-yl-idenemethyl)-phenothiazine(6)via elimination in an alkaline medium,followed by hydrogenation with palladium-black to give mequitazine.The structure of target compound was confirmed by IR,1H-NMR and 13C-NMR,and the overall yield was 41.9%.The improved method was easy for synthesis and suitable for industrial manufacturing.更多还原