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

A synthesis method and amino acid ester technology, applied in asymmetric synthesis, organic chemistry methods, chemical instruments and methods, etc., can solve the problems of poor chemical selectivity, troublesome post-processing, complex products, etc., and achieve simple synthesis methods and convenient post-processing , good chemoselective effect

Inactive Publication Date: 2010-11-24
UNIV OF JINAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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 amo

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Taking the preparation of L-phenylalanine methyl ester as an example, the specific operations are as follows:

[0026] Mix 0.5 mol of 2-pyridinecarbaldehyde and L-phenylalanine methyl ester with methanol as a solvent, react for 2 hours at normal temperature and pressure, then add 8g of 5% Pd / C catalyst to the reaction mixture, and The catalytic hydrogenation reaction was carried out in an autoclave, the hydrogen pressure was 0.3 MPa, and the reaction was carried out for 48 hours.

[0027] The reaction mixture was filtered under reduced pressure, the Pd / C catalyst was recovered, and then the solvent methanol was removed by rotary evaporation, and a certain amount of chloroform was added as a solvent to wash and purify the crude product. First wash with hydrochloric acid solution, then wash with sodium hydroxide solution to neutralize the hydrochloric acid, and finally wash with saturated brine. The organic phase was dried by adding anhydrous magnesium sulfate, filtered ...

Embodiment 2

[0029] Taking the preparation of L-leucine methyl ester as an example, the specific operation is the same as in Example 1 to obtain an orange-red liquid, namely the product N-(2-pyridylmethyl)-L-leucine methyl ester, with a total yield of 76.5%. [α] D 14 -25.1° (chloroform, c=1), the purity is above 97% by high performance liquid chromatography.

Embodiment 3

[0031] The molar ratio of the feed material is 2-pyridinecarbaldehyde:L-phenylalanine methyl ester is 1.2:1, other operations are the same as in Example 1, the yield is 80%, and the purity analyzed by high performance liquid chromatography is more than 97%.

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PUM

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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 ...

Claims

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Application Information

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IPC IPC(8): C07B53/00C07D213/74
Inventor 崔玉孙国新尹少宏夏光明游淇
Owner UNIV OF JINAN
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