Method for preparing ofloxacin

Abstract

The invention discloses a method for preparing ofloxacin. The invention aims to provide a method for preparing ofloxacin, which has short production period, less pollution, high raw material utilization rate, yield and purity, and simple and convenient operation. The method comprises the following steps: preparing 9,10-difluoro-2,3-dihydro-3-methyl-7-O-7H-pyridino[1,2,2-de]-[1,4]- benzoxazinyl-6-carboxylic acid by tetrafluorobenzoyl chloride as a raw material through a compounding method; and reacting with alkali in an organic solvent to obtain the ofloxacin. The invention has the advantages that the tetrafluorobenzoyl chloride reacts with 3-(2-R1-2-R2-4- methylimidazole alkyl) acrylic ester, the product is directly hydrolyzed during post processing and then is carried out the ring close;the reaction step is reduced, the reaction time is shortened, and the yield is as high as 85-90 percent. Organic or inorganic alkali is added in preparation, thereby reducing the feed content of methyl piperazine, reducing the reaction cost and having high yield.

Description

technical field [0001] The present invention relates to the production technology of medicine, specifically a kind of preparation method of ofloxacin. Background technique [0002] Ofloxacin is an antibiotic, which has achieved great success in clinical anti-infection treatment due to its high-efficiency, broad-spectrum, and low-toxicity antibacterial properties. [0003] [0004] The synthesis research and process of ofloxacin have been continuously improved and improved in the past two decades, and the current main production methods are as follows: [0005] 1. Using 2,3,4,5-tetrafluorobenzoic acid as the starting material, such as patent US4777253, 1988, through acid chloride, and EtOMgCH (CO 2 Et) 2 Condensation decarboxylation, condensation with triethyl orthoformate, substitution with aminopropanol, cyclization, condensation with methylpiperazine, hydrolysis, and purification. The steps are long and the yield is low. The total yield is only about 21%. [0006] 2....

AI Technical Summary

Problems solved by technology

[0005] 1. Using 2,3,4,5-tetrafluorobenzoic acid as the starting material, such as patent US4777253, 1988, through acid chloride, and EtOMgCH(CO 2 Et) 2 Condensation decarboxylation, condensation with triethyl orthoformate, aminopropanol substitution, cyclization, condensation with methylpiperazine, hydrolysis, refining, long steps, low yield, the total yield is only about 21%

[0006] 2. Using trifluoronitrobenzene or its derivatives as raw materials, such as patent US4382892, 1983, through selective alkali hydrolysis, etherification, reduction, salt formation, and (CH 3 ) 2 NCH=C(CO 2 Et) 2 Condensation, cyclization, hydrolysis, connection with N-methylpiperazine, and refining, the total yield is only 14%, and there are many three wastes, so it is not easy for industrial production