Ethanol → Valproic Acid

Participants

Reaction Steps

A mixture of 38.6 ml of 70% methanesulfonic acid and 352.2 g of diethyl dipropylmalonate was heated to 135°-145° C. in a flask equipped with a distillation column packed with Raschig rings. After 1.5 hour, ethanol began to reflux in the distillation head. Ethanol was distilled as it formed and the pot temperature was maintained at 120°-145° C. by periodic addition of water to the pot. After 5 hours, additional ester (133 g) was added to the pot and the distillation of ethanol was continued. After 24 hours, the distillation of ethanol had ceased. The mixture then was cooled and treated with 50 ml of water. The layers were separated and the organic layer was washed with 100 ml of 5% sodium chloride solution to afford 257.6 g (90% yield) of valproic acid as a light brown liquid.

Provenance & Evidence