Synthesis Of Intermediate Of Rivastigmine And Process Of Ring-opening Fluorination Of Betamethasone Epoxies

This dissertation consists of two parts.The synthesis of key intermediate of Rivastigmine and the process of ring-opening fluorination of Betamethasone epoxies were discussed in the first and second part respectively.In the Chapter one of Part I,the introduction of Rivastigmine was presented and the progress of the asymmetric synthesis of chiral Rivastigmine was emphasized.In the Chapter two of Part I,one key intermediate3-(1-(dimethylamino)ethyl)phenol with acetophenone as starting material via nitration,hydrogenation,diazotization hydrolysis and substitution was designed.The optimization of the hydrogenation reaction catalyzed by Pd/C and the hydrolysis of diazonium salt were studied.Another key intermediate,N-ethyl-N-methylcarbamoylchloride was synthesized from N-methylethylamine through chloroformylation.The racemic Rivastigmine was synthesized by condensation of these two key intermediates.This method has following advantages:(1)it is easy to operate;(2)the use of expensive reagents was avoided;(3)the volume of waste water was reduced;(4)it is suitable for industrial application.In the Chapter one of Part II,the introduction the Betamethasone was presented and the progress of ring-opening fluorination of Betamethasone epoxies was emphasized.In the Chapter two of Part II,a method of ring-opening fluorination of Betamethasone epoxies with HF-TfOH-[Bmim]OTf/toluene as catalytic fluorination system was explored at-30 ~oC~-25 ~oC.The optimization of the amount and recycling of solvent were also studied.The results revealed that the usage of hydrofluoric acid was reduced,the yield and purity was improved and the cost was declined.With this method,the waste water was reduced,and the environmental problems in industrial production can be easily solved.