氧氟沙星的合成改进

A modified synthetic route of ofloxacin

采用 2 ,3,4-三氟硝基苯为原料和 2 -羟甲基 - 2 -甲基 - 1,3-二氧五环缩合、水解得醚酮 ,收率 90 %。再经雷尼镍氢化 ,乙氧亚甲基丙二酸二乙酯 (EMME)缩合 ,再经硫酸、乙酐环合 ,加水水解得羧酸物 ,收率75 %。羧酸物与 N-甲基哌嗪缩合、精制得氧氟沙星 ,收率 85 %,总收率 5 7.4%。

A modified synthetic route of ofloxacin (1) was presented. 2,3,4-trifluoro-nitrobenzene as starting material, reacted with 2-hydroxy- methyl-2-methyl-1,3-dioxane and then hydrolyzed to give 2-acetony-loxo-3,4-difluoro-nitrobenzene (5) with a yield of 90%. Catalyzed by ReyNi, (5) was hydrogenated to give 7,8-difluoro-2,3-dihydro-3-methyl-4H-1,4-benzoxazine (6). 6 was condensed with EMME, then after cyclization in the presence of concentrated sulfuric acid and acetic anhydride, water was added dropwise under cooling and then hydrolyzed by refluxing to give (±)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido -1,4-benzoxazine-6-carboxylic acid (9) with a yield of 75%. (8) was reacted with N-methyl piperazine in DMSO to give (±)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3- dihydro-7H-pyrido -1,4-benzoxazine-6-carboxylic acid (1) of 85% yield. And the overall yield of ofloxacin (1) was 57%.