Method for synthesizing benserazide hydrochloride by utilizing fixed bed hydrogenation equipment

Abstract

The invention discloses a method for synthesizing benserazide hydrochloride by using fixed bed hydrogenation equipment, which is characterized in that a compound 1 reacts with an amino protective agent to carry out an amino protection reaction, so that the subsequent purification is easy, and the dosage of hydrazine hydrate in the synthesis method is small; according to the method, fixed bed hydrogenation equipment is used for synthesis, a fixed bed reactor is filled with a solid catalyst or a solid to realize a heterogeneous reaction process, the catalyst in the fixed bed reactor is relatively fixed, a reaction liquid flows through a bed layer, and the reaction liquid flows through the bed layer by adjusting the flow rate and the reaction pressure; qualified products can be obtained after reaction liquid flows out of the fixed bed, continuous production can be achieved, product deterioration caused by long-time contact of the products and the catalyst can be avoided, the same amount of products can be produced due to continuous production, the reactor size can be very small, the safety problem caused by high-pressure reaction is greatly reduced, the amount of the catalyst used in the reaction is less, and the production cost is reduced.

Description

technical field [0001] The invention relates to the field of chemical industry, in particular to a method for synthesizing benserazide hydrochloride by utilizing fixed-bed hydrogenation equipment. Background technique [0002] Benserazide hydrochloride is a peripheral decarboxylase inhibitor, which is often combined with levodopa in the pharmaceutical market to make a compound preparation dopasrazide for the treatment of Parkinson's disease. [0003] Benserazide hydrochloride is white or off-white crystalline powder, easily soluble in water, slightly soluble in methanol, insoluble in ethanol or acetone. It is extremely unstable and sensitive to changes in solvent pH, light, temperature and humidity. [0004] In the prior art, the synthesis of benserazide generally first synthesizes benserazide, and then reduces benserazide to benserazide, which has some disadvantages: (1) the crude product of methyl serine is recrystallized with water and ethanol, and the production cycle i...

AI Technical Summary

Problems solved by technology

[0006] In order to overcome the above-mentioned technical problems, the object of the present invention is to provide a method for synthesizing benserazide hydrochloride using fixed-bed hydrogenation equipment: by using DL-serine and thionyl chloride as starting materials for esterification to generate compound 1 , carry out the amino protection reaction of compound 1 and amino protecting agent at a reaction temperature of 20-30°C to obtain compound 2, carry out amine transesterification reaction of compound 2 and hydrazine hydrate, after the reaction is completed, use hydrochloric acid to adjust the pH of the reaction system Value, concentrated to remove excess hydrazine hydrate, then adjusted to acidity, added alcohols to crystallize to obtain compound 3, compound 3 and 2,3,4-trihydroxybenzaldehyde were condensed in an ethanol water system to generate compound A, Compound A is subjected to post-processing steps to obtain compound 4, compound 4 is hydrogenated in a fixed-bed reactor, the solvent is concentrated, alcohols are added, crystallized to generate compound B, and compound B is subjected to post-processing steps to obtain compound 5, Compound 5 is subjected to a salt-forming reaction to obtain compound 6, which is benserazide hydrochloride, which solves the problem of high-pressure reactions in the production process of existing benserazides, and there are serious safety hazards in high-pressure reactions. The amount of catalyst used in the process is large, and the catalyst is in contact with the product, which is easy to cause the problem of product deterioration

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