一种左氧氟沙星半水合物合成工艺的改进

An Improvement for the Synthesis Process of Levofloxacin Hemihydrate

以(S)-(-)-9,10-二氟-2,3-二氢-3-甲基-7-氧代-7H-吡啶并[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯(左氟环合酯)为起始原料,与4-甲基哌嗪缩合得(S)-(-)-9-氟-2,3-二氢-3-甲基-10-(4-甲基-1-哌嗪基)-7-氧代-7H-吡啶并[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯,再经氢氧化钠水解,乙醇结晶得左氧氟沙星半水合物;合成工艺操作简单,所用试剂种类少,对环境污染小,适合工业化生产。

The starting material of Ethyl(S)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylate(levofloxacin and ester)is reacted with 4-methyl piperazine to obtain(S)-(-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperaxinyl)-7-oxo-7H-py-ridino[1,2,3-de][1,4]benzoxazine-6-carboxylate,and then hydrolyzed with sodium hydroxide crystallized with ethanol to obtain Levofloxacin hemihydrate。The operation is simple。Few reagents are used.There is little pollution to the environment。The methond is suitable for industrial large-scale production。