1、隨矗殛墑@天畢大謦中國(guó)i苣代第一所大學(xué)工程碩士學(xué)位論文iLIL^爿舊111]31joml0IIH2410Iei腳j省F：11[I]0i領(lǐng)域：制藥工程作者姓名：王艷波指導(dǎo)教師：張瑛教授企業(yè)導(dǎo)師：聶文輝高級(jí)工程師天津大學(xué)研究生院2006年5月ABSTRACTTheaimofthisstudywastoobtainprocessparametersforindustrialproductionoflevofloxacinmesylateThe

2、chiral(S))2aminopropanolwassynthesizedfromLlactamicacidAndthenlevofioxacinmesylatewassynthesizedfrom23，4，5一tetrafluorobenzoicacid(S)()一2aminopropanolwasobtainedfromLlactamicacidviaesterificationandreductionreactionsLlact

3、amicacidwithbiochemicalpurltyWasselectedasstartingmaterial111eoptimalconditionsforesteriflcationwereLlactamicacidandthionylchridemixtureinmoleratio1：11，thedropwisingtemperaturecontrolledbetween0and5“C，andreactionkeptat38

4、40(2for4hThereductionWasundertakenwitllmoleratioofthesubstrateandpotassiumborohydrideat1：2LevonoxacinmesylateWassynthesizedfrom2，3，4，5一tetrafluoro；benzoicacidviaacylchlorination，condensationpartialhydrolysisanddecarboxyl

5、ization，aminationcyclization，andtosylateformationTheacylchlorinationWasrakedin4hatrefuxDiethylmalonatecondensationwascontrolledatthetemperaturebetween10to50CThepartialhydrolysisanddecarboxylizationfor6handthetriethylorth

6、oformatecondensationfor4hwerefinishedTheaminationcyclizationWasreacted證tllthesubstrateand(S)()2一aminopropanolinthemoleratioof1：107at904CforlOhDimethylsulfoxidewasthebestsolventintheNmethylpiperazinecondensationWithexcess

7、ivesulfonicacid，themixtureoflevofloxacin，purifiedwaterandactivecarbonintheratioof1：4：01(g：ml：g)washeatedat60“Cfor15rainforpurification，Theoverallyieldoflevofioxacinmesylatewas3925％witllthisnewprotocolwhilereferenceyielda

8、s35％ThedataofIRandNMRconfirmedthecompositionandstructureThequalityoftheproductmetthespecificationofWSl一(XlS7)2003ZTheremarkableadvantagesofthenewprocesswereofmildreactiveconditions，simpleoperationandexcellentreproducibil