[Synthesis of S-(+)-rivastigmine hydrogentartrate].
OBJECTIVE
To optimize the synthetic procedure of S-(+)-rivastigmine hydrogentartrate which was known as an agent for the treatment of Alzheimer disease.


METHODS
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.


RESULTS
The total yield of S-(+)-rivastigmine hydrogentartrate was 4.17%.


CONCLUSIONS
The materials in this procedure are all commercially available. The reaction conditions are mild and total yield is high.
Feng
Jin
J
Department of Medicinal Chemistry, School of Pharmacy, Jinan University, Guangzhou 510632, China.
Chen
Wei-Min
WM
Sun
Ping-Hua
PH
D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D048448:Phenylcarbamates / Q000138:chemical synthesis* / Q000737:chemistry; D000068836:Rivastigmine; D013237:Stereoisomerism
D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D000068836:Rivastigmine