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Synthesis method of chiral alpha-amino acid ester derivative

A technology of amino acid esters and synthetic methods, applied in the direction of asymmetric synthesis, organic chemical methods, chemical instruments and methods, etc., to achieve the effects of mild conditions, simple operation, and good industrial practicability

Active Publication Date: 2021-01-29
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this method is only suitable for a small number of substrates

Method used

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  • Synthesis method of chiral alpha-amino acid ester derivative
  • Synthesis method of chiral alpha-amino acid ester derivative
  • Synthesis method of chiral alpha-amino acid ester derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065]

[0066] Under nitrogen protection, [Ir(COD)Cl] 2 (0.002mmol, 0.5mol%), chiral ferrocene skeleton phosphine-phosphoramidite ligand (0.0048mmol, 1.1mol%) was dissolved in tetrahydrofuran (1.0mL), stirred at room temperature for 10 minutes, added substrate (4- Methoxyphenylimino) tetrahydrofuran (1.0mL) solution of methyl phenylacetate (0.4mmol) and 5.1mg iodine are placed in an autoclave, replaced by hydrogen for 3 times, and then fed with hydrogen to 50 atmospheres , reacted at 25°C for 24 hours. Hydrogen gas was released slowly, and the product was separated with a silica gel column after removing the solvent.

[0067] The product is detected and analyzed, and the NMR and HPLC data are as follows:

[0068] Yellow oil was obtained in 96% yield after purification with column chromatography on silica gel (hexanes / ethyl acetate,10 / 1).92%ee was determined by chiral HPLC (Chiralcel OJ-H, n-hexane / i-PrOH=70 / 30 ,0.8ml / min,254nm,40℃):t R (minor) = 26.8min,t R (major) = ...

Embodiment 2

[0071] With the reaction condition H among the embodiment 1 2 The pressure was changed to 100 atmospheres, and the rest were the same as in Example 1 to obtain the product. After testing, the product was (4-methoxyanilino) methyl phenylacetate, with a yield of 98% and an enantioselectivity of 92% ee.

Embodiment 3

[0073] With the reaction condition H among the embodiment 1 2 The pressure was changed to 20 atmospheres, and the rest were the same as in Example 1 to obtain the product. After testing, the product was (4-methoxyanilino)methyl phenylacetate, with a yield of 76% and an enantioselectivity of 90% ee.

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Abstract

The invention discloses a synthesis method of a chiral alpha-amino acid ester derivative. The chiral alpha-amino acid ester derivative is prepared by catalyzing asymmetric hydrogenation of imino acidester by taking a complex prepared in situ through reaction of a chiral ferrocene skeleton phosphine-phosphoramidite ligand and a metal iridium precursor as a catalyst. And a feasible way is providedfor amino acid synthesis. Compared with other methods for synthesizing chiral amino acid ester, the method has the advantages that the chiral ferrocene skeleton phosphine-phosphoramidite ligand for hydrogenation is simple to synthesize, low in price and suitable for kilogram-level production, the iridium / chiral ferrocene skeleton phosphine-phosphoramidite system is high in catalytic activity and enantioselectivity, and the enantiomeric excess value (ee value) of the product is up to 96% or above; the method is simple in hydrogenation reaction operation, mild in condition, high in atom economyand suitable for industrial production, has a good result on synthesis of phenylglycine ethyl ester, reaches a yield of 92% and enantioselectivity of 91%, and has good industrial practicability.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a synthesis method of chiral α-amino acid ester derivatives, which is suitable for the production of unnatural amino acids. Background technique [0002] Chiral amino acids and their derivatives are important intermediates in chemicals, pharmaceuticals, and biosynthesis, and play a vital role in protein and peptide research. The most concise and convenient methods for the synthesis of chiral amino acid esters include asymmetric hydrogenation of dehydrogenated amino acid esters and asymmetric hydrogenation of α-imidate esters. Among them, the asymmetric hydrogenation of α-imidate is a green, environmentally friendly and efficient method for the synthesis of chiral aromatic amino acid esters. With the help of chiral catalysts and other auxiliary agents, it directly hydrogenates α-imidate substrates to generate chiral aromatic amino acid ester compounds. In recent years, great pro...

Claims

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Application Information

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IPC IPC(8): C07B53/00C07C227/06C07C229/28C07C229/36C07D333/24
CPCC07B53/00C07C227/06C07D333/24C07B2200/07C07C229/36C07C229/28
Inventor 胡向平胡信虎
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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