Bitartrate Rivastigmine And Galantamine Synthesis

The present paper primary task involves the research on rivastigmine hydrogentanrate and galanthamine's synthesis, mainly includes the following works:1. A Novel Synthesis Process of Rivastigmine HydrogentanrateThis chapter focuses on the synthesis of rivastigmine hydrogentanrate. Currently rivastigmine was synthesized from two intermediates of N-ethyl-N-methyl-amino-acid chloride and 3-[(1- dimethyl amino)ethyl]phenol, which also could be syntheseized with different ways. According the literatures, synthesis method was improved based on the reported route. Fitstly, benzaldehyde and procedures solution were used as the starting materials. N-ethyl-N-methyl carbamate chlorobenzoyl chloride was synthesized after methylation, hydrolysis, neutralization. Secondly, 3-[1-(dimethylam- ino)ethyl]phenol was synthesized from 1-(3-Hydroxyphenyl)ethanone and DMF at high temperature. Then (S)-3-[1-(dimethylamino)ethyl] phenol was isolated. Lastly, rivastigmine was synthesized from the two intermediates and then was reacted with L-(+)-tartaric acid to give the target compound. The route has many advantages such as low cost, high yield and easy to operate and suitable for industrial production.2. The Synthesis Research of GalanthamineGalantamine hydrobromide is a highly selective acetylcholinesterase inhibitor. It is mainly used for the treatment of Alzheimer's disease. 3, 4-Dimethoxybenzaldehyde was used as the starting material. The nitryl group, a strong electron withdrawing group, is designed as a placeholder group. After demethylation and nitration, 2-nitro-5-hydroxy-4-methoxybenzaldehyde yieided was react with tyramine to give a shoft base. N-(4-hydroxy-ethyl)-N-(2-nitro-5-hydroxy-4-Aoxybenzyl)formamide was synthesized from the shoft base after reduction and amidation. The key intermediate of N-(4-hydroxyethyl)-N-(2-nitr-5-hydroxy-4-methoxy-methyl)formamide was synthesized by oxidative cyclization reaction with potassium ferricyanide as Oxidants. Then racemic galanthamine was lastly synthesized with steps of reaction.