Synthetic method of escitalopram impurity J

Abstract

The invention discloses a synthetic method of an escitalopram impurity J, belonging to the technical field of medicaments. The synthetic route comprises the steps of using escitalopram oxalate as a raw material, adding an acid-binding agent into a solvent in the presence of hydrogen peroxide, and performing hydrolysis reaction to generate the escitalopram impurity J. The method disclosed by the invention uses escitalopram oxalate as a starting material; compared with a raw material required by a conventional method, escitalopram oxalate has the advantages of low cost and easy purchase; the synthetic route is simple, only needs a one-step reaction, is mild in reaction conditions and small in pollution caused by a reagent and the solvent adopted in the reaction, and has the characteristic of environmental friendliness; the escitalopram impurity J synthesized by the synthetic method is high in purity and yield.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a synthesis method of escitalopram impurity J. Background technique [0002] Escitalopram is the L-isomer of citalopram, and its efficacy is 100 times that of the D-isomer of citalopram. As a new generation of antidepressants, it is mainly suitable for major depression and generalized anxiety (GAD) The treatment of psychiatric diseases and other mental diseases has the advantages of rapid onset of effect, fewer drug interactions and adverse reactions, and stable drug efficacy. The future development prospect is very bright. Therefore, it is of great significance to develop high-quality escitalopram raw materials and preparations. Since the research on drug impurities is very important in drug process research, optimization and quality control, the research on escitalopram impurities is also very necessary. [0003] The following is the structure of escitalopram imp...

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Problems solved by technology

[0008] This synthesis method has the following disadvantages: high temperature reflux is required in the synthesis, and when the reaction time is too long or the alkalinity is too strong, the cyano group is easily hydrolyzed into acid; the reaction operating conditions are difficult to control, so the reaction yield is low and the selectivity is poor , the post-treatment is cumbersome; this technology only converts the racemic citalopram hydrobromide into a racemic amide compound, and does not obtain the S-configuration escitalopram impurity J

[0011] This synthetic method has the following disadvantages: firstly, the reaction raw material needs to be obtained by hydrolysis of citalopram, and the route is relatively long; thionyl chloride and ammonia which are more serious to environmental pollution are used in the synthesis, and tail gas treatment is required; acid chlorides are easy to hydrolyze and can be Friedel-Crafts acylation reaction takes place, produces by-product, and reaction selectivity is not good, makes the productive rate of amidation only 45%; The same method just converts citalopram hydrobromide into racemic amide compound, also does not obtain S-configuration escitalopram impurity J

[0012] In summary, the existing methods all use the hydrolysis of the cyano group of citalopram under alkaline conditions or the acid chlorination and amination of the racemic acid to obtain the amide of the racemate, but no single optical isomer is obtained. , and the cyano group is easily hydrolyzed under alkaline conditions to generate excessive hydrolysis by-product carboxylic acid, carboxylic acid acid chloride, amination method, the reagents used are more toxic, and there are more by-products, the reaction selectivity is not good, and the post-treatment is difficult

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