The Production Procession Analysis Of Levofloxacin Hydrochloride For Pharmaceutical Raw Materials

Quinolones are one kind of synthetic antibacterial drugs, which have a wide antimicrobial spectrum, high antibacterial activity, and low resistance. These drugs are mainly used in the treatment of urogenital system infections, intestinal infections, respiratory infections, skeletal system infection, skin soft tissue infection, etc. The applications of the quinolones make them become one of the most important antibiotics.Levofloxacin, one of the fourth generations of quinolones, is the national essential drugs and one of the most important fluoroquinolone drugs which exhibits good therapeutic effect on respiratory infection, urinary reproductive system infection and skin soft tissue infection. To find a procedure with simple process, mild conditions, low cost, less pollution and higher yield way as soon as possible to synthesize levofloxacin, which is suitable for our national industrial conditions, is become more and more important.2,3,4,5-tetrafluorobenzoic chloride is one of the important drug intermediates, which can be obtained with4-chloroaniline by amination, chlorination and hydrolysis, decarboxylation. The procedure with four steps reactions is a good method with simple process, mild conditions, low cost, less pollution and higher yield way as soon as possible to synthesize levofloxacin, which is suitable for our national industrial conditionsN, N-dimethyl amino ethyl acrylate, with polymerized vinyl and activity of large tertiary amine. can undertake a variety of reactions and is the key intermediates to synthesize quinolones skeleton. However, the synthesis methods of N, N-dimethyl amino ethyl acrylate are not suitable for large-scale industrial production because of the high price of raw material, the complicated process, and the low yield. Thus, it is significant for the development and production of quinolones to solve these problems.2,3,4-trifluoronitrobenzene is not only an important intermediates for synthesis of fluoroquinolone drugs, but also plays a very important role on other synthetic field. It can be directly synthesized via nitration and fluorination from1,2,3-trichlorobenzene with simple procedure and less reaction steps. However, the price of1,2,3-trichlorobenzene is high, and the yield is too low. Thus it’s necessary to optimize the production process to realize its industrialization.Although levofloxacin has many synthetic routes, the most suitable way for industrial production currently is from the reaction of N, N-dimethyl amino ethyl acrylate and2,5-tetrafluorobenzoic four fluorine benzene chloride through a four steps reaction to provide the key intermediates((S)-(-)-9-two hydrogen fluoride-2,3-2-3-methyl-7-oxygen generation-7-hydrogen pyridine and [1,2,3-DE][1,4] oxazine-benzene and6-carboxylic acid ethyl ester). Then the levofloxacin could be obtained in two steps. The reaction process is short and yield is high. However, this process also has drawbacks, such as price of N, N-dimethyl amino ethyl acrylate is high, intermediate reaction generated the gas dimethylamine which can lead to the atmospheric pollution. The optimization of the route is helpful for the development of pharmaceutical production.