Study On Synthesis Of Brexpiprazole And Ceftibuten Intermediates

This thesis consists of four chapters:The first chapter firstly introdu-ced the schizophrenia and the classification and research progress of anti-psychotic drugs.Then R&D of synthetic methods for the preparation of Brexpiprazole intermediate was reviewed.Finally,the content and signif-icance of the research are defined.In the second chapter,according to the relevant literatures,we optimized the synthesis process of the intermedia-tes of brexipiprazole.We investigated the effects of temperature,catalyst loading etc.on the reaction and obtained the optimum reaction process.Route 1 took 2,6-dichlorobenzaldehyde as starting material,the desired product 4-chlorobenzo[b]thiophene was synthesized in a total yield of 77%by cyclization,hydrolysis,decarboxylation,and the purity was 99%determined by HPLC.The cost of raw materials was reduced and proced-ure was improved.Route 2 took 2-chloro-6-fluorobenzaldehyde as starti-ng material which was cheap and readily available.The desired product 1-(benzo[b]thiophen-4-yl)piperazine was synthesized in a total yield of 57%by coupling reaction with tertbutoxycarbonyl piperazine,cyclizati-on,hydrolysis,decarboxylation,and the purity of product was 99%deter-mined by HPLC.This route use molecular sieve as catalyst for C-N Cou-pling,avoiding the use of noble metal catalysts(such as palladium)and tertiary phosphine ligands.The new process can be more easily applied in industry.In third chapter we firstly introduced the research status of ?-la-ctam antibiotics as well as its classification and mechanism of action.Th-en reviewed the synthesis methods of Ceftibuten and intiermediate.Fina-lly,according to the relevant literatures,we optimized the synthetic proc-ess of the Ceftibuten intermediate in the fourth chapter.In this experiment,we focused on making a preliminary exploration about the synthesis of Ceftibuten intermediate.The reaction conditions,such as the ratio and ad-ding order of rectants,reaction temperature,reaction time and solvents,c-atalysts were investigated.