Method for preparing homopiperazine by utilizing ethyl trifluoroacetate

Abstract

The invention discloses a method for preparing homopiperazine by utilizing ethyl trifluoroacetate. The method comprises the following steps: (1) taking ethylenediamine as an initial raw material; enabling the ethylenediamine to react with the ethyl trifluoroacetate under the action of an organic solvent, so as to prepare bistrifluoroacetylethylenediamine; (2) enabling the bistrifluoroacetylethylenediamine obtained by the step (1) to react with a 1,3-disubstituted propane compound under the action of a solvent and a catalyst, so as to obtain bistrifluoroacetyl homopiperazine; (3) enabling the bistrifluoroacetyl homopiperazine obtained by the step (2) to react with a hydrogen chloride ethanol solution to obtain homopiperazine bihydrochloride; recycling the ethyl trifluoroacetate; (4) enabling the homopiperazine bihydrochloride obtained by the step (3) to react with alkali under the action of a solvent and a catalyst, so as to prepare the homopiperazine. The method disclosed by the invention has the beneficial effects of simplicity and convenience for operation, relatively low cost, relatively high yield, relatively small pollution and wide applicable range, and can meet the requirements on industrial production of products.

Description

technical field [0001] The present invention relates to a process for the preparation of homopiperazines. Background technique [0002] Homopiperazine is an aza seven-membered ring compound and is an important pharmaceutical intermediate. Most of its derivatives have strong biological activity and medicinal value, and can be used to synthesize homopiperazine hydrochloride, cyclizine, carbamate, etc. Medications such as mazepine, quinolones, and chlorocyclazine. Drugs such as quinoline and isoquinoline derivatives, quinolone derivatives, and thiazolidine hydroxy acid amide derivatives modified with homopiperazine as raw materials are useful for the treatment of cardiovascular diseases, interstitial plasma cell pneumonia, especially for AIDS patients. Interstitial plasma cell pneumonia, asthma, central nervous system disorders including depression and anxiety have shown good efficacy. For example, 1-(5-isoquinolinesulfonyl)homopiperazine hydrochloride can effectively treat s...

AI Technical Summary

Problems solved by technology

However, this method has two very obvious disadvantages: the first is that the used protective reagent benzenesulfonyl chloride cannot be recycled, and a large amount of waste will be generated. Usually, the production of one ton of homopiperazine will generate at least two tons of solid waste that cannot be recycled. The second is that in the process of deprotecting group, it is necessary to use highly corrosive and highly polluting concentrated sulfuric acid or hydrobromic acid, which is very corrosive to equipment and will cause great harm to the health of operators. relatively poor security

This method has the same disadvantages as the previous method, and the reaction temperature is higher during deprotection, which is more dangerous and not suitable for industrial production.

[0010] In view of the above-mentioned processes for preparing homopiperazine, there are many three wastes, high risk of deprotection reagents, and poor operation safety. Therefore, it is of great significance to find a green industrial production method for synthesizing homopiperazine.

Images