Method for synthesizing 5-benzylazaspiro[2,4]heptane

Abstract

The invention relates to a method for synthesizing 5-benzylazaspiro[2,4]heptane. The method comprises the following steps of: making N-benzylpyrrolidone (compound 1) react with 2-benzyloxyiodoethane in the presence of lithium diisopropylamide to generate 3-benzyloxyethylN-benzylpyrrolidone; and carrying out hydroxyl protective reaction and reacting with methane sulfonyl chloride to generate methane sulfuryl ester, performing intramolecular nucleophilic substitution in the presence of lithium hexamethyldisilaneamine to generate 4-oxo-5-benzylazaspiro[2,4]heptane, and reducing through lithium aluminum hydride to obtain 5-benzylazaspiro[2,4]heptane. The method has the advantages of concise route, reasonable process, simple and readily-available raw materials, low cost, convenience in post-treatment, high total yield and easiness in amplifying. Due to the adoption of the method, the defects of long synthesizing route, low total yield, high operation complexity, difficulty in post-treatment, difficulty in amplifying and the like existing in the conventional literature process are overcome.

Description

technical field [0001] The invention relates to a practical synthesis method of 5-benzylazaspiro[2,4]heptane. Background technique [0002] 5-benzylazaspiro[2,4]heptane can be debenzylated to obtain 5-azaspiro[2,4]heptane, which is an important intermediate in organic synthesis, and its derivatives Has high biological activity, the latest research shows that these derivatives have anti-CNS disorders in addition to the activity of anti-Grass-positive and Grass-negative bacteria (Arch.Pharm.Chem.Life Sci., 2007,340,530). The destruction of the cognitive system caused by it, such as Alzheimer's disease (EP1961750, WO2011018495). In recent years, by linking 5-azaspiro[2,4]heptane to some specific structures to seek some active screening Drugs have become one of the hotspots in medicinal chemistry. [0003] The synthetic method of 5-benzylazaspiro[2,4]heptane mainly generates benzylamine acetoacetate through the condensation of ethyl acetoacetate and benzylamine, and then forms...

AI Technical Summary

Problems solved by technology

There are the following disadvantages: 1. The synthetic route is long, and 8 steps are required before and after the reaction, resulting in low overall yield, troublesome post-processing, and cannot be produced on a large scale. 2

Reagents such as liquid bromine and hydrazine hydrate are needed, which have high requirements on the corrosion resistance of the reaction equipment, which is not conducive to environmental protection. 3. The reduction of carbonyl hydrazine hydrate needs to be carried out at high temperature

Images