丙戊酸杂质47

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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. was heated to 135°-145° C. in a flask equipped with a distillation column to reflux in the distillation head Ethanol was distilled as it formed After 5 hours the distillation of ethanol After 24 hours the distillation of ethanol The mixture then was cooled treated with 50 ml of water The layers were separated the organic layer was washed with 100 ml of 5% sodium chloride solution

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 70 g of p-toluenesulfonic acid monohydrate, 140 g of diethyl dipropylmalonate and 9 ml of water was heated to reflux in a flask equipped with a distillation column packed with Raschig rings. Ethanol was distilled as it formed and the pot temperature was maintained at 120°-155° C. by periodic addition of water to the pot. After 5 hours, 25 ml of water had been added and the evolution of ethanol had nearly stopped. The mixture was maintained at 140° C. for 18 hours and then was cooled and treated with 100 ml of water. The layers were separated to afford 72.2 g (87.8% yield) of valproic acid as a light brown liquid. The water layer was washed with 50 ml of toluene and the toluene was combined with the crude valproic acid layer. Vacuum distillation afforded a colorless valproic acid fraction (72 g, 87% yield) boiling at 132° C./28" Hg. was heated to reflux in a flask equipped with a distillation column Ethanol was distilled as it formed was cooled The layers were separated

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 70 g of p-toluenesulfonic acid monohydrate, 140 g of diethyl dipropylmalonate and 9 ml of water was heated to reflux in a flask equipped with a distillation column packed with Raschig rings. Ethanol was distilled as it formed and the pot temperature was maintained at 120°-155° C. by periodic addition of water to the pot. After 5 hours, 25 ml of water had been added and the evolution of ethanol had nearly stopped. The mixture was maintained at 140° C. for 18 hours and then was cooled and treated with 100 ml of water. The layers were separated to afford 72.2 g (87.8% yield) of valproic acid as a light brown liquid. The water layer was washed with 50 ml of toluene and the toluene was combined with the crude valproic acid layer. Vacuum distillation afforded a colorless valproic acid fraction (72 g, 87% yield) boiling at 132° C./28" Hg. was heated to reflux in a flask equipped with a distillation column Ethanol was distilled as it formed was cooled The layers were separated

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 70 g of p-toluenesulfonic acid monohydrate, 140 g of diethyl dipropylmalonate and 9 ml of water was heated to reflux in a flask equipped with a distillation column packed with Raschig rings. Ethanol was distilled as it formed and the pot temperature was maintained at 120°-155° C. by periodic addition of water to the pot. After 5 hours, 25 ml of water had been added and the evolution of ethanol had nearly stopped. The mixture was maintained at 140° C. for 18 hours and then was cooled and treated with 100 ml of water. The layers were separated to afford 72.2 g (87.8% yield) of valproic acid as a light brown liquid. The water layer was washed with 50 ml of toluene and the toluene was combined with the crude valproic acid layer. Vacuum distillation afforded a colorless valproic acid fraction (72 g, 87% yield) boiling at 132° C./28" Hg. was heated to reflux in a flask equipped with a distillation column Ethanol was distilled as it formed was cooled The layers were separated