Process for preparing N-methyl homopiperazine from 2-haloethylamine compound

Abstract

The invention discloses a process for preparing N-methyl homopiperazine from 2-haloethylamine compound, and the process comprises the following steps: Step 1, taking the 2-halogenated ethylamine compound as a raw materia to react with ethyl trifluoroacetate to obtain N-(2-Haloethyl) trifluoroacetamide; Step (2) taking the N-(2-Haloethyl) trifluoroacetamide as a raw material to react with methylamine or methylamine hydrochloride to obtain N-methyl-N'-trifluoroacetyl ethylenediamine; Step (3) taking the N-methyl-N'-trifluoroacetyl ethylenediamine as a raw material to react with 1,3-disubstituted propane compound to obtain N-methyl-N'-trifluoroacetyl homopiperazine; Step (4) taking the N-methyl-N'-trifluoroacetyl homopiperazine as a raw material to react with a hydrogen chloride ethanol solution to obtain N-methyl homopiperazine dihydrochloride; and Step (5) taking the N-methyl homopiperazine dihydrochloride as a raw material to prepare the N-methyl homopiperazine by alkalization. The process has the advantages of simple operation, low cost, high yield, low pollution and suitability for industrialized production.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a process for preparing N-methylhomopiperazine by utilizing 2-halogenated ethylamine compounds. Background technique [0002] N-methylhomopiperazine is an aza seven-membered ring compound and an important pharmaceutical intermediate. Most of its derivatives have strong biological activity and medicinal value. According to the query results on Reaxys, there are currently 193 international patents using N-methylhomopiperazine to develop various new drugs such as antibacterial drugs and cardiovascular drugs, and its application prospects are very promising. [0003] At present, the mature method for preparing N-methylhomopiperazine in large quantities currently only has the following synthetic route: [0004] Using N-methyl-4-piperidone as a raw material, it is condensed with hydroxylamine hydrochloride first, then rearranged by Beckmann, and finally reduced ...

AI Technical Summary

Problems solved by technology

This method has two very obvious disadvantages: the first is that lithium aluminum hydride needs to be used for reduction, the heat release is violent, the danger is very high, and the generated aluminum salt waste residue is also particularly large; the second is the repeatability of the entire route. Relatively poor, the yield is extremely unstable in the actual production process

[0006] In view of the above-mentioned technology for preparing N-methylhomopiperazine, there are many three wastes, the risk of reducing reagents is relatively large, and the operation safety is poor.

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