Preparation method for levofloxacin-N-oxide

Abstract

The invention provides a preparation method for levofloxacin-N-oxide and relates to the field of a levofloxacin medicament. The preparation method comprises the following steps of: mixing the levofloxacin and 0.1mol / L hydrochloric acid solution according to a proportion of 0.03mol: 500ml, and dissolving the mixture at the temperature of between 80 and 100 DEG C; adding 100ml of hydrogen peroxide solution having the mass concentration of 30 percent by three times at the temperature of between 60 and 80 DEG C; reacting for 3 to 5 hours each time to obtain reaction solution; drying the reaction solution through distillation; and recrystallizing the residual water. The selection of the raw materials is convenient for the subsequential separating operation; by adding the hydrogen peroxide solution in steps, the progress of the reaction is controlled, the generation of byproducts is reduced, the conversion rate of the levofloxacin-N-oxide is improved and the generation of impurities is reduced; and by the method, the condition is easy to control, the route is simple, the solvent is obtained easily, the yield is 88.7 percent, the cost of the levofloxacin-N-oxide serving as a contrast is reduced greatly, and the product purity is high and over 99.5 percent, so the levofloxacin-N-oxide can be used as a working contrast.

Description

technical field [0001] The invention relates to the field of medicine levofloxacin, in particular to a preparation method of levofloxacin-N-oxide. Background technique [0002] Levofloxacin is the left-handed form of ofloxacin, which has the characteristics of broad antibacterial spectrum and strong antibacterial effect. Japan's Daiichi Pharmaceutical Co., Ltd. launched levofloxacin raw materials and tablets in Japan in 1993, and is now on the market in the United Kingdom, the United States and other countries. Levofloxacin preparations currently on the market in China mainly include tablets, small needles, glucose injections and eye drops. At present, many documents at home and abroad have reported the known impurities of ofloxacin, but there are few research reports on the known impurities of levofloxacin. However, it can be inferred from the known impurities of ofloxacin and the synthesis route that levofloxacin probably contains the same For process impurities with t...

AI Technical Summary

Problems solved by technology

The degradation product produced by placing in H2O2 contains levofloxacin-N-oxide, CAS number 178964-53-9, molecular formula C18 H20FN3O5, molecular weight 377, chemical name: 4-[(S) 6-carboxy-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de ]-1,4-Benzoxazin-10-yl]-1-methylpiperazine-1-oxide, the English name is 4-[(S)-6 -carboxy-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1 ,4-benzoxazine-10-yl]-1-methylpiperazine 1-oxide, although the structure of this impurity has been reported in foreign literature, but there is no public report on its preparation method at home and abroad

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