6-氰基-1-羟基-7-甲基-5-氧-3,5-二氢中氮茚-2-羧酸甲酯的合成工艺改进

Improved synthesis of 6-cyano-1-hydroxy-7-methyl-5-oxo- 3,5-dihydro-indolizine-2-carboxylic acid methyl ester

目的改进喜树碱全合成关键中间体 6 氰基 1 羟基 7 甲基 5 氧 3,5 二氢中氮茚 2 羧酸甲酯 (4)的合成工艺。方法通过控制滴速与反应时间 ,提高了乙酰丙酮酸乙酯的产率 ,并由该化合物以“一锅煮”的方法制备了化合物 4。结果总收率由 31%提高到 4 2 5 %。结论新工艺简化了操作、提高了收率、缩短了反应时间、减少了试剂的用量。

Aim To improve the synthesis of 6-cyano-1-hydroxy-7-methyl-5-oxo-3,5-dihydro-indolizine-2-carboxylic acid methyl ester,an intermediate of the total synthesis of camptothecins.Methods Under control of the speed of dropping and reaction time,the yield of ethyl acetopyruvate was raised,and 'one-pot procedure' was taken to prepare the title compound from ethyl acetopyruvate.Result The overall yield of the title compound was raised from 31% to 42.5%.Conclusion The operation is simplified,the yield is raised,the reaction time is shortened and the usage of the reagent is reduced.