ChemicalBook CAS DataBase List Rivastigmine

Rivastigmine synthesis

10synthesis methods

Product Name:Rivastigmine
CAS Number:123441-03-2
Molecular formula:C14H22N2O2
Molecular Weight:250.34

42252-34-6 Synthesis

42252-34-6
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123441-03-2
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$9.00/10mg

Yield:123441-03-2 86.6%

Reaction Conditions:

Stage #1:(S)-3-(1-dimethylaminoethyl)phenol with sodium hydride in diethyl ether at 20; for 1 h;
Stage #2:N-ethyl-N-methylcarbamoyl chloride at 20; for 3 h;Reactivity;

Steps:

2 Preparation of S-(-)-rivastigmine (II)
150 ml of diethylether are placed in a 0.51-three-neck flask and sodium hydride as a 60% dispersion in oil (0.48 g) is added slowly under inert conditions (Ar or N2) and stirring. A suspension develops, to which crystalline compound (III) (2.0 g, 0.012 mol) is added at room temperature. After stirring for one hour, a slightly turbid solution of the phenolate forms, to which 1.53 g (0.012 mol) OF N-ETHYL-N-METHYLCARBAMOYLCHLORIDE in 20 ml of ether are added dropwise at room temperature. The resulting reaction mixture is stirred at room temperature for 3 hours. Thereafter, it is diluted with 100 ml of water. The organic layer is separated and extracted with 2x 50 ml of a 0.1 N NAOH solution. The organic phase is extracted with 50 ml of water, dried with anhydrous magnesium sulfate, and concentrated in vacuo. 2.6 g of an oil are obtained (86.6% of the theoretical yield).

References:

ZENTIVA, A.S. WO2004/37771, 2004, A1 Location in patent:Page 13