Synthesis method for novel chiral asymmetric secondary amine belonging to N-substituted amino acid esters

Abstract

The invention relates to a synthesis method for novel chiral asymmetric secondary amine belonging to N-substituted amino acid esters. The method of the invention comprises two major steps: (1) amino acid ester firstly reacts with aldehyde to form an imine intermediate; and (2) in situ reduction is carried out on the imine intermediate to form asymmetric secondary amine, wherein the reduction utilizes a Pd / C catalytic hydride process. The reaction product is separated and purified to obtain the novel chiral asymmetric secondary amine belonging to the N-substituted amino acid esters. The synthesis method solves the problem that the direct primary amine alkylate method most commonly used in asymmetric secondary amine synthesis has poor chemical selectivity, and avoids the problems that alkylation reaction is generated to produce a great amount of byproducts of tertiary ammonium and quaternary ammonium, a great amount of unreacted raw material primary amine exists, the aftertreatment is difficult and the yield is low. Compared with the amide reduction method for preparing the asymmetric secondary amine, the method of the invention has the advantages of less reaction steps, simple operation, no by-products, high yield and the like.

Description

technical field [0001] The invention relates to a compound synthesis method, in particular to a synthesis method of N-substituted amino acid ester novel chiral asymmetric secondary amine. Background technique [0002] More than half of the world's drugs are amine or amide compounds, and amine compounds widely exist in nature as important biologically active substances. The amine group is not only the key active group of modern drugs, but also the amine-based compounds, especially secondary amines, are also important intermediates and ligands in organic synthetic chemistry. Therefore, the synthesis of secondary amines occupies a very important position in the fields of medicinal chemistry and organic synthetic chemistry. Secondary amines are highly polar, difficult to handle, and unstable to oxidation. The research on the synthesis of secondary amines has always been one of the hotspots of synthetic chemists. [0003] The synthesis of unsymmetrical secondary amines usually ...

AI Technical Summary

Problems solved by technology

The disadvantage is that the chemical selectivity is poor, the alkylation reaction inevitably occurs, and the product is complex. In addition to the formation of secondary amines, a large amount of tertiary amines and quaternary ammonium salt by-products are also produced, and there are also a large amount of unreacted raw material primary amines. Troublesome handling, low yield