Synthesis process for sodium valproate

Abstract

The invention discloses a synthesis process for sodium valproate. The synthesis process comprises the following steps: mutually dissolving diethyl malonate and 1-bromopropane, slowly adding the obtained mixture into an ethanol solution of sodium ethoxide at a certain temperature, carrying out heating and reflux for 2 h, recovering ethanol until temperature is 110 DEG C, carrying out cooling to less than 80 DEG C, adding a certain amount of water to dissolve sodium bromide, carrying out layering to obtain a plurality of layers, then adding an aqueous sodium hydroxide solution with a concentration of 15 to 30%, carrying out hydrolysis at 60 to 70 DEG C for 3 h, then carrying out heating to recover ethanol until a gas phase temperature is 99 DEG C, carrying out cooling to less than 80 DEG C, adding hydrochloric acid for neutralization and acidifying, adding crude valproic acid to dissolve dipropylmalonic acid so as to obtain mixed acid and subjecting the mixed acid to slow heating and decarboxylation at 110 to 160 DEG C for production of crude valproic acid; and subjecting the crude valproic acid to rectification and refining, adding a certain amount of the aqueous sodium hydroxide solution for neutralization, adding toluene for reflux to bring out water, thereby allowing sodium valproate to dehydrate and crystallize and then successively carrying out filtering, washing with chloroform and drying so as to obtain finished sodium valproate. The process is safe and environment-friendly, produces good-quality sodium valproate, has low cost and is suitable for industrial production.

Description

technical field

[0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a synthesis process of sodium valproate. Background technique

[0002] The synthetic process of sodium valproate includes at least basic processes such as regulating extraction, rectification, stirring, and drying. In the current technical process method for preparing sodium valproate, the technical process is not easy to implement, the sodium valproate produced has low purity, the single-pass conversion rate of reactants is low, the production process is complicated, the production efficiency is low and the cost is high, so it is not suitable for large-scale production. mass production. Contents of the invention

[0003] In order to overcome the above-mentioned technical problems existing in the prior art field, the object of the present invention is to provide a kind of synthetic technique of sodium valproate, the present invention not only manufac...

Examples

Embodiment

[0015] The synthetic technique of the sodium valproate of the present embodiment may further comprise the steps:

[0016] (1) Diethyl malonate and 1-bromo-n-propane are dissolved in each other, and the mixture is slowly added to the ethanol solution of sodium ethoxide at 50°C;

[0017] (2) Heat up and reflux for 2 hours, recover ethanol to 110°C, cool down to 80°C, add a certain amount of water to dissolve NaBr;

[0018] (3) Add 30% aqueous sodium hydroxide solution to the organic layer after layering, and hydrolyze at 60°C for 3 hours;

[0019] (4) Raise the temperature to recover ethanol until the gas phase temperature reaches 99°C, cool down to 80°C, add hydrochloric acid to neutralize and acidify;

[0020] (5) Add crude valproic acid to dissolve dipropylmalonic acid to form a mixed acid;

[0021] (6) Slowly heat up at 110°C for decarboxylation to generate crude valproic acid. After the crude valproic acid is refined by rectification, it is neutralized by adding a quantit...

technical field

[0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a synthesis process of sodium valproate. Background technique

[0002] The synthetic process of sodium valproate includes at least basic processes such as regulating extraction, rectification, stirring, and drying. In the current technical process method for preparing sodium valproate, the technical process is not easy to implement, the sodium valproate produced has low purity, the single-pass conversion rate of reactants is low, the production process is complicated, the production efficiency is low and the cost is high, so it is not suitable for large-scale production. mass production. Contents of the invention

[0003] In order to overcome the above-mentioned technical problems existing in the prior art field, the object of the present invention is to provide a kind of synthetic technique of sodium valproate, the present invention not only manufac...

Examples

Embodiment

[0015] The synthetic technique of the sodium valproate of the present embodiment may further comprise the steps:

[0016] (1) Diethyl malonate and 1-bromo-n-propane are dissolved in each other, and the mixture is slowly added to the ethanol solution of sodium ethoxide at 50°C;

[0017] (2) Heat up and reflux for 2 hours, recover ethanol to 110°C, cool down to 80°C, add a certain amount of water to dissolve NaBr;

[0018] (3) Add 30% aqueous sodium hydroxide solution to the organic layer after layering, and hydrolyze at 60°C for 3 hours;

[0019] (4) Raise the temperature to recover ethanol until the gas phase temperature reaches 99°C, cool down to 80°C, add hydrochloric acid to neutralize and acidify;

[0020] (5) Add crude valproic acid to dissolve dipropylmalonic acid to form a mixed acid;

[0021] (6) Slowly heat up at 110°C for decarboxylation to generate crude valproic acid. After the crude valproic acid is refined by rectification, it is neutralized by adding a quantit...