A kind of preparation method of diphenylmethylamine hydrochloride

Abstract

The invention provides a preparation method of azelnidipine starting material ethylamine benzhydrylamine. The method comprises the step of using benzophenone and formamide as raw materials to carry out aLeuckart reaction. The catalyst of silicon dioxide is added into a reaction system, and thus the reaction time is drastically reduced, wherein the time is decreased to 3-4 h from 8 h, and therefore energy consumption is significantly reduced; the rough product yield of a compound II is dramatically increased and is up to 96-98%. The purity of HPLC is not lower than 96.5%, so that it is ensured that after the ethylamine benzhydrylamine obtained by hydrochloric acid hydrolysis is purified once, the yield can reach 80%, the purity is not lower than 99.9%, and the ethylamine benzhydrylamine is quite suitable for industrial production.

Description

technical field [0001] The invention relates to a method for preparing diphenylmethylamine hydrochloride, a key starting material of azedipine, by using an improved Leuckart reaction, and belongs to the technical field of medicine. Background technique [0002] Diphenylmethylamine hydrochloride is the starting material for the preparation of azedipine, which is stable to high temperature, high humidity and light, while the free diphenylmethylamine has poor stability and cannot be stored for a long time. There are three main synthetic routes of existing reports of diphenylmethylamine hydrochloride (or free base): [0003] (1) Oxime reduction method [0004] [0005] This route takes benzophenone as starting material, and it reacts with hydroxylamine to form oxime, and then obtains benzhydrylamine through reduction. The oxime reduction methods reported in the literature include reducing reagent reduction and high-pressure hydrogenation reduction, and the reducing reagents...

AI Technical Summary

Problems solved by technology

[0013] (1) The reaction temperature is high and requires a temperature above 180°C to react;

[0014] (2) The reaction time is relatively long, usually more than 8 hours, and the energy consumption is high;

[0015] (3) The conversion rate of the reaction is low, and many impurities are generated, which leads to the yield of compound II below the middle level (60%);

[0016] (4) The purity of diphenylmethylamine hydrochloride obtained through hydrolysis is not high;

In the disclosed reaction system, the molar ratio of benzophenone, formic acid and formamide is 1:1.9:18.3, and the amount of formamide is too large, resulting in a large amount of waste liquid after the reaction, which is not conducive to environmental protection requirements and cost control

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