Synthesis of S-(+)-rivastigmine hydrogentartrate / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To optimize the synthetic procedure of S-(+)-rivastigmine hydrogentartrate which was known as an agent for the treatment of Alzheimer disease.</p><p><b>METHODS</b>S-(+)-rivastigmine hydrogentartrate was synthesized by using 1-(3-hydroxyphenyl)ethanone as the starting material via oximation, reduction and N-methylation to produce the key intermediate 3-1-dimethylaminoethylphenol, which finally reacted with N-ethyl-N-methylcarbamoyl chloride. The enantiomers were resolved with di-(+)-p-toluoyl-D-tartaric acid, and the title compound was prepared by mixing S-rivastigmine base with L-(+)-tartrate.</p><p><b>RESULTS</b>The total yield of S-(+)-rivastigmine hydrogentartrate was 4.17%.</p><p><b>CONCLUSION</b>The materials in this procedure are all commercially available. The reaction conditions are mild and total yield is high.</p>