Synthesis method of 3-aminopyrrolidine dihydrochloride

Abstract

The invention discloses a synthetic method of 3-aminopyrrolidine dihydrochloride. The synthetic method comprises the following steps: preparing benzyl-(3-ethoxy-3-alkenyl)-(1-vinyl ethoxy methyl) amine liquid; preparation of a 1-benzyl-3-pyrrolidone solution; preparation of a 1-benzyl-3-aminopyrrolidine solution; preparing a 1-benzyl-3-aminopyrrolidine salt; preparing a 3-aminopyrrolidine solution; the yield and purity of the 3-aminopyrrolidine dihydrochloride are improved by controlling the activity of the reaction main materials of each part in a segmented manner and carrying out a directional hydrogenation manner.

Description

technical field [0001] The invention relates to a synthesis method of 3-aminopyrrolidine dihydrochloride. Background technique [0002] 3-aminopyrrolidine dihydrochloride and its optical isomers are key intermediates in the synthesis of a large number of drugs. The optically active 3-aminopyrrole dihydrochloride is a key intermediate for the preparation of agricultural chemicals such as vinylpyrrolidone-cephalosporin derivatives and pharmaceutical active substances tosufloxacin and other quinolone antibacterial drugs. [0003] Japanese patent application JP61057579A reports: N-ethoxycarbonylglycine ethyl ester is first added to ethyl acrylate, followed by Dieckmann ring closure, followed by selective hydrolysis and decarboxylation to obtain pyrrolidone. In 3-aminopyrrolidine. [0004] Japanese open patent JP3133954A reports: N-benzylglycine ethyl ester first adds ethyl acrylate, then carries out Dieckmann ring synthesis under the presence of t-BuOK to obtain N-benzyl-4-for...

AI Technical Summary

Problems solved by technology

[0005] In the synthetic routes disclosed in Japan, there are the following problems: 1. The reaction route is long, with many steps, the total yield is low, and the pollution is large; 2. Some reaction routes involve oxime formation reactions, resulting in lower yields; 3. The reaction conditions during debenzylation are harsh, high temperature and high pressure are not easy to control; the industrial production cost of 3-aminopyrrolidine is too high

[0006] Chinese patent application CN2006101501116 discloses a synthetic method for preparing 3-aminopyrrolidine using benzylamine, ethyl acrylate, and ethyl chloroacetate as main starting materials through addition, cyclization, hydrolysis, and hydrogenation (two steps). ; avoid the generation of oxime intermediates, and improve the yield relative to the method disclosed in Japan, and obtain a new synthesis method with simple technology and low cost; but due to the high reactivity of raw materials, although the yield increases, the yield of the product The yield is unstable, and the by-products 3-hydroxypyrrolidinol, 4-aminopiperidine, and 3-methylaminopyrrolidine appear, and the output of by-products is unstable; the purity of the product is improved by distillation and purification of organic solvents, which increases the synthesis cost

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