Synthetic method for intermediate diethyl diethylmalonate of barbiturate

Abstract

he invention provides a synthetic method for an intermediate, i.e., diethyl diethylmalonate, of barbiturate. The synthetic method comprises the following steps: adding 1.13 mol of ethanolamine and 0.5 mol of cuprous chloride into a reaction vessel and controlling a stirring speed to be 130 to 160 rpm; after complete dissolving of ethanolamine, adding 0.65 mol of diethyl malonate drop by drop within 2 to 3 h; heating a solution obtained in the previous step to 70 to 75 DEG C and maintaining the heating state for 50 to 70 min; carrying out cooling, wherein a solid is precipitated; then adding 1.1 to 1.3 mol of ethylamine drop by drop within 2 to 3 h and maintaining a reflux state for 4 to 5 h; adding 300 ml of a potassium chloride solution and decreasing the temperature of the solution to 5 to 8 DEG C; carrying out extraction with cyclohexane three to five times and combining extract; successively carrying out washing with a salt solution, dehydrating with a dehydrating agent and evaporation of cyclohexane; then carrying out pressure-reduced distillation and collecting a fraction obtained at a temperature of 185 to 195 DEG C; and subjecting the fraction to re-crystallization in acetonitrile so as to obtain a crystal, i.e., diethyl diethylmalonate; wherein the mass fraction of the potassium chloride solution is 15 to 20%, the mass fraction of cyclohexane is 80 to 85%, and the salt solution is any one selected from a group consisting of sodium nitrate and potassium sulfate.

Description

technical field

[0001] The invention relates to a method for synthesizing barbiturate intermediate diethylmalonate. Background technique

[0002] Barbiturates have sedative, hypnotic, anticonvulsant and antiepileptic effects. It can also be used as a pre-anesthesia drug, and when used in combination with antipyretic and analgesic drugs, it can enhance the analgesic effect of the latter. In recent years, it has been reported that this product can be used to prevent neonatal hyperbilirubinemia and kernicterus, and can also treat cholestasis. After adding phenobarbital to patients with cerebral edema, cerebral edema and herniation improved quickly, blood pressure was easily stabilized, and cerebral vasospasm and rebleeding were also reduced. Oral administration of this product combined with intramuscular injection of chorionic gonadotropin treats primary infertility. It can also treat polycystic ovum syndrome and reduce the incidence of intracranial hemorrhage in premature i...

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