Study On Synthesis Of Cefcapene

Cefcapene acid is a third generation cephalosporin derivative which has broad spectrum antibacterial action for both gram-positive and gram-negative bacteria.It also has highly stability for ?-lactamase which can hydrolyse antibiotics.Cefcapene acid is the active ingredients of Cefcapene Pivoxil Hydrochloride in the human body,and also an important impurity affecting the quality during the production process.Therefore developing a simple,practical,high quality,high yield and low-cost synthetic process of Cefcapene acid has great significance.In Chapter ?,we introduced the history,antibacterial properties,current situation in domestic and foreign markets of Cefcapene pivoxil hydrochloride.And we also stated that Cefcapene acid was the major impurity which affected the terminal product's quality during the production and application process.In Chapter ?,we mainly summarized the synthetic route before,and selected the method which used 7-ACA as the starting material to produce Cefcapene acid through the process of basic hydrolysis,reacting with the Boc-protected side chain,amino formylation,salification and deprotection.We optimized the hydrolytic process of 7-ACA,obtaining the best experiment protocol by using mixed bases for hydrolysis and controlling the appropriate pH value during crystallization,and then tried the pilot test of this technique.We optimized the condensation condition of parent nucleus and side chain,confirming the reaction time by HPLC.Then we compared the post-processing program of the condensation product and chose the program of using it in the next step directly.We screened the organic base for the synthesis of BCN and the dropping time of chlorosulfonate isocyanate in the amino formylation step,then confirmed the operable range of this process.In addition,we tried the destructive test of BCN,obtaining the condition that the major impurity generated and summarized the pilot plant test results.Finally,we screened the deprotective reagent,and got cefcapene acid with a total yield of 59% and HPLC purity of 97.6%.