A kind of preparation method of high-purity difenidol hydrochloride

Abstract

The invention discloses a preparation method of high-purity difenidol hydrochloride. The method is to dissolve the intermediate α,α-diphenyl-1-piperidine butanol in one of acetone, ethyl acetate, tetrahydrofuran, butanone, acetonitrile or dichloromethane; and then Raise the temperature to 40-45°C, add activated carbon, mix and stir for 0.5-1h; filter while hot, keep the filtrate at 40-45°C, then add hydrochloric acid solution dropwise at a rate of 2mL / min-8mL / min until the pH of the solution is 4-45°C 6. Then continue to keep warm for 1~2h; then lower the temperature to 20~25°C and keep warm for 1~2h, then lower the temperature to 5~10°C and stir for 2~4h, then difenidol hydrochloride can be precipitated. The preparation method of the present invention is not only simple, has low requirements for instruments and equipment, and has low production cost, but also the prepared target product has few types of impurities and low content, the molar yield of the product into salt is over 90%, and the purity is over 99.8%. , the impurity benzhydryl alcohol is controlled below 0.05%, while the alkene compound impurity is controlled below 0.05%, and the content of total impurities is below 0.1%.

Description

technical field [0001] The invention relates to the technical field of medicine, and more specifically, relates to a preparation method of high-purity difenidol hydrochloride. Background technique [0002] The chemical name of Diphenidol Hydrochloride is 1,1-diphenyl-4-(1-piperidinyl)-1-butanol hydrochloride, which is the main component of Vertigo, and Diphenidol Hydrochloride can improve vertebral base Insufficient arterial blood supply, expansion and spasm of blood vessels, adjustment of vestibular nervous system, inhibition of abnormal impulse of vestibular nervous system, inhibition of vomiting center and medullary emetic chemoreceptor area, with peripheral weak anticholinergic effect, difenidol hydrochloride is widely used in Anti-vertigo and anti-emetic, can be used to treat Meniere's disease, after ear surgery (labyrinthitis) and motion sickness, can improve nystagmus, and can also prevent and treat dizziness or nausea and vomiting caused by various diseases and drugs...

AI Technical Summary

Problems solved by technology

The preparation of this patent uses a single solvent isopropanol as a salt-forming solvent, which is conducive to the recycling of solvents, but the viscosity and boiling point of isopropanol may easily lead to excessive residual solvents in the product; it is not conducive to the removal of benzphenyl alcohol, a Grignard by-product. ; There is no filtration step in the whole refining process, which may lead to excessive inorganic impurities in the product. At the same time, inorganic impurities may affect the crystallization of the product, thereby affecting the yield of the finished product, the content of impurities and the purity of the product

In addition, this method adjusts the pH of the solution=3, which may lead to the generation of alkylene compounds (the generation of alkylene compounds is shown in the following reaction formula): Finally, the content of olefinic impurities is more, and the purity of the target product is reduced

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