Research On The Novel Process For Synthesis Of Key Intermediates Of Levofloxiacin

Levofloxacin have listed for more than 20 years,although in the face of fierce market competition,it still“got it”for the exact clinical efficacy and slight side effects.China is a major exporter of levofloxacin API,whether it is from the perspective of environmental protection,or in order to control costs,the research on the preparation process of levofloxacin is still in full swing.Based on a comprehensive review of the synthetic routes of levofloxacin,a new process for the Levofloxacin carboxylic acid,the key intermediate of Levofloxacin,was designed and studied.This novel process put forward with methyl N,N-dimethylamino acrylate instead of ethyl N,N-dimethylamino acrylate for the first time,in order to avoid using instability and the difficulty of preparation of sodium ethoxide.The synthesis process of methyl N,N-dimethylamino acrylate was also studied in this paper,under the optimal conditions,the purity could reach99%.Control the use and storage of carbon monoxide,this process could be a low-cost and simple route.The substitution of key start material ethyl N,N-dimethylamino acrylate,put forward new requirements of reaction conditions on new process.Obviously,methyl acrylate is more susceptible to hydrolysis in the cyclization process,so that the reaction becomes more impurities.This study found that with K₂CO₃ as the base,the yield of cyclization reaction was up to 85.6%and the purity was99.4%at 130?.The appropriate HPLC test conditions were established for each step reaction of the new process,and the structure of the reaction intermediates and final product was confirmed.