Preparation process of lavo-ofloxacin and ofloxacin

Abstract

The invention relates to a preparation process of lavo-ofloxacin and ofloxacin which are anti-infectious medicaments, belonging to the synthetic process with tetrafluorobenzoic aid as raw material. The preparation method is characterized in that (2, 3, 4, 5-phenyl tetrafluoride formyl) ethyl acetate and DMFA react for 1.0-1.5h in toluene at 50-55 DEG C with the existence of acylating catalyst; the reaction product is washed by water, and an aqueous layer is separated; at 30-35 DEG C, L-amino propanol is dripped in an oil layer to carry out replacement reaction for 1.5-2.0h; toluene is decompressed, recovered and dried proper quantity of DMF is added to the oil layer for diluting; the diluted oil layer is dripped into back-flow DMF with the existence of anhydrous potassium fluoride to carry out back-flow reaction for 6h; DMF is recovered, water is added for centrifugation, acid is added to the obtained solid to be hydrolyzed to prepare lavo-perfluorocarboxylic acid, the lavo-perfluorocarboxylic acid reacts with N-methyl piperazine in DMSO at 90-110 DEG C by taking triethylamine as an acid-binding agent, and the lavo-ofloxacin is obtained after the fine purification of the product of reaction. The process improves the reaction condition of (2, 3, 4, 5-phenyl tetrafluoride formyl) ethyl acetate and DMFA, lowers the reaction temperature, shortens the reaction time and improves the reaction yield of lavo-fluoro ester serving as a reaction intermediate by 20 percent.

Description

technical field [0001] The invention belongs to the technical field, in particular to a preparation method of levofloxacin and ofloxacin. Background technique [0002] Fluoroquinolones have achieved great success in clinical anti-infection treatment due to their high-efficiency, broad-spectrum, and low-toxic antibacterial properties. Ofloxacin and levofloxacin developed by Japan's Daiichi Pharmaceutical Company are excellent representative drugs. [0003] Levofloxacin, English name: Leovfloxacin, molecular formula: C 18 h 20 FN 3 o 4 1 / 2H 2 O, its structural formula is as follows: [0004] [0005] Ofloxacin, English name: Floxacin, molecular formula: C 18 h 20 FN 3 o 4 , its structural formula is as follows: [0006] [0007] Levofloxacin synthesis, the route reported in the literature mainly contains the following three: [0008] 1. The early route is mostly split method: including high performance liquid phase split EP206283 (1986) and enzyme split method...

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Problems solved by technology

[0020] However, during the reaction between intermediate (V) and DMFA, the reaction time is long, and impurities are generated more, and the liquid phase content of product (XIII) in the reaction solution is only 76-80%

Moreover, it has been found through research that when the reaction temperature is reduced to 60°C, the reaction rate is significantly reduced, and after 10 hours, about 10% of (V) still remains; and when the temperature is raised above 80°C, the reaction rate increases, but the side reactions also increase soon

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