Improvement method for synthesis process of memantine hydrochloride

Abstract

The invention discloses an improvement method for a synthesis process of memantine hydrochloride; with 1,3-dimethyl adamantane as a raw material, 3,5-dimethyl-1-adamantanol is obtained through a bromination reaction and a hydrolysis reaction; 3,5-dimethyl-1-adamantanol is subjected to a chlorination reaction to obtain 1-chloro-3,5-dimethyl adamantane; and 1-chloro-3,5-dimethyl adamantane is subjected to an ammoniation reaction, acid hydrolysis and salt formation, and the target product of methamine hydrochloride is produced, wherein in the bromination reaction, the reaction molar ratio of 1,3-dimethyl adamantane and bromine is 1:1.1, the reaction is performed in dichloroethane, and after the hydrolysis reaction, an organic phase is separated and washed to remove bromine and washed and dried, and an obtained solution is directly used for a next reaction. The improvement method provided by the invention can improve the yield, increase reaction safety and reduce waste and waste water.

Description

technical field [0001] The invention relates to an improved synthesis process of memantine hydrochloride, which belongs to the technical field of chemical synthesis. Background technique [0002] Memantine hydrochloride is a drug for the treatment of dementia developed by the German Merz company. It is a novel, low-moderate affinity, voltage-dependent, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. It can non-competitively block NMDA receptors, reduce the excessive excitation of NMDA receptors caused by glutamate, prevent cell apoptosis, and improve memory. It is a new generation of drugs for improving cognitive function. In February 2002, the European Patent Medicines Committee (CPMP) approved it for the treatment of patients with moderate and severe Alzheimer's disease. It was launched in Germany in August of the same year, and was approved by the US Food and Drug Administration ( FDA) approved for the treatment of patients with moderate to severe Alzhei...

AI Technical Summary

Problems solved by technology

[0006] In the method, the amount of bromine used in the first step reaction is relatively large, and the molar ratio of bromine to 1,3-dimethyladamantane is 2:1, and more bromide by-products will be produced after excess bromine is treated. And use diethyl ether as extraction solvent, safety is low; The second step reaction uses concentrated hydrochloric acid yield on the low side (80%), contains more water in the concentrated hydrochloric acid, influences reaction to carry out to positive direction; In the 3rd step aftertreatment, adopt Chloroform is a solvent extraction, and chloroform is highly toxic; the yield in the fourth step is only 74%, and the concentrated hydrochloric acid contains more water, and many products cannot be separated out after being dissolved in water

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