Potassium Hydroxide → Etiracetam, (R)-

Participants

Reaction Steps

6.2 g (0.03 mole) of (R)-N-[1-(aminocarbonyl)propyl]-4-chlorobutanamide and 0.484 g (0.0015 mole) of tetrabutylammonium bromide are mixed in 42 ml of dichloromethane at 0° C. under a nitrogen atmosphere. 2.02 g (0.036 mole) of potassium hydroxide powder are added over 30 minutes at such a rate that the temperature of the reaction mixture does not exceed +2° C. The mixture is stirred for 15 minutes and then allowed to return to ambient temperature. The insoluble material is filtered off and the filtrate concentrated under reduced pressure. The residue obtained is stirred in 25 ml of carbon tetrachloride for 30 minutes, and then filtered off and dried. The product is recrystallized in 45 ml of ethyl acetate in the presence of 1.7 g of 0,4 nm molecular sieve. The latter is removed by hot filtration to give 3.85 g of (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide. Melting point: 116°-118° C. [alpha]D25 : +89.8° (c=1, acetone). Yield: 75.4%.

Provenance & Evidence