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Preparation method of N-(5-methoxycarbonyl-2-hydroxyphenyl) amino acid ester compounds

A technology of ester compounds and hydroxyphenyl, which is applied in the field of preparing N-amino acid ester compounds, can solve the problems of harsh reaction conditions, high reaction temperature, complex catalytic system, etc., and achieves no need for noble metal catalysis, mild reaction conditions and sustainable development. The effect of preparation

Active Publication Date: 2014-11-26
GUANGZHOU CHEM CO LTD CHINESE ACADEMY OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The main disadvantage of the above-mentioned first method is that the reaction conditions are relatively harsh, and higher reaction temperature and longer reaction time are often required, and strong bases, expensive heavy metal catalysts and ligands need to be used; the latter two methods have the difficulties of obtaining raw materials, Disadvantages such as poor substrate adaptability, complex catalytic system, and low yield
At present, there is no successful report on the N-arylation of amino acid compounds using non-aromatic compounds as raw materials

Method used

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  • Preparation method of N-(5-methoxycarbonyl-2-hydroxyphenyl) amino acid ester compounds
  • Preparation method of N-(5-methoxycarbonyl-2-hydroxyphenyl) amino acid ester compounds
  • Preparation method of N-(5-methoxycarbonyl-2-hydroxyphenyl) amino acid ester compounds

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] The preparation of N-(5-methoxycarbonyl-2-hydroxyl phenyl)-L-alanine methyl ester comprises the following steps:

[0032]Get 3-dehydroshikimate methyl ester (0.93g, 5.0mmol), anhydrous aluminum trichloride (0.03g, 0.25mmol), 10g3A molecular sieves in reaction flask, the ethanol solution of 20mlL-alanine methyl ester ( 0.77g, 5.5mmol L-alanine methyl ester hydrochloride and 0.30g, 5.5mmol sodium methoxide in ethanol) were added to the above reaction flask. The above reaction system was reacted at 70° C. for 6 h, followed by TLC. After completion of the reaction, cool, filter, and remove the solvent by rotary evaporation, column chromatography, eluting with ethyl acetate-petroleum ether, and concentrating to remove the solvent to obtain a light yellow oily liquid (([α] 25 / D =-63.79, c=0.59 dehydrated alcohol) 1.03g, yield: 82%.

[0033] The structural characterization data of the product are as follows: 1 HNMR (400MHz, DMSO-d 6 )δppm: 10.40(s,1H),7.19(dd,J 1 =8.15,J ...

Embodiment 2

[0035] The preparation of N-(5-methoxycarbonyl-2-hydroxyl phenyl) glycine methyl ester comprises the following steps:

[0036] Get 3-dehydroshikimate methyl ester (0.93g, 5.0mmol), p-toluenesulfonic acid (0.05g, 0.25mmol), 10g3A molecular sieves in reaction flask, the methanol solution of 20ml glycine methyl ester (0.69g, 5.5mmol Glycine methyl ester hydrochloride and 0.30 g, 5.5 mmol of sodium methoxide in methanol) were added to the above reaction flask. The above reaction system was reacted at 65° C. for 12 h, followed by TLC. After the reaction was completed, it was cooled, filtered, and the solvent was removed by rotary evaporation. Column chromatography, eluting with ethyl acetate-petroleum ether, recrystallized to obtain 0.99 g of a light yellow solid, yield: 83%. m.p.110-112°C.

[0037] The structural characterization data of the product are as follows: 1 HNMR (400MHz, DMSO-d 6 )δppm: 10.36(s,1H),7.18(dd,J 1 =8.00,J 2 =1.74Hz,1H),6.89(d,J=1.74Hz,1H),6.75(d,J=8.00...

Embodiment 3

[0039] The preparation of N-(5-methoxycarbonyl-2-hydroxyl phenyl)-L-isoleucine methyl ester comprises the following steps:

[0040] Take 3-dehydroshikimate methyl ester (0.93g, 5.0mmol), acetic acid (14.30μl, 0.25mmol), 10g3A molecular sieves in a reaction flask, and 20ml of L-isoleucine methyl ester ethanol solution (1.00g, 5.5mmol L-isoleucine methyl ester hydrochloride and 0.30g, 5.5mmol sodium methoxide in ethanol) were added to the above reaction flask. The above reaction system was reacted at 70° C. for 6 h, followed by TLC. After the reaction was completed, it was cooled, filtered, and the solvent was removed by rotary evaporation, and column chromatography was eluted with ethyl acetate-petroleum ether, and recrystallized to obtain a light yellow solid (([α] 25 / D =-83.80, c=0.28 absolute ethanol) 1.18g, yield: 80%. m.p.109-111°C.

[0041] The structural characterization data of the product are as follows: 1 HNMR (400MHz, DMSO-d 6 )δppm: 10.47(s,1H),7.19(dd,J 1 =8....

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Abstract

The invention discloses a preparation method of N-(5-methoxycarbonyl-2-hydroxyphenyl) amino acid ester compounds. The method comprises the steps of allowing reaction of N-arylation reagent and amino acid methyl ester in presence of organic solvent, catalyst and dehydrating agent; cooling product after reaction, filtering, concentrating, separating and / or recrystallizing to obtain N-(5-methoxycarbonyl-2-hydroxyphenyl) amino acid ester compounds. The N-arylation reagent is methyl 3-dehydroshikimate, ethyl 3-dehydroshikimate or propyl 3-dehydroshikimate; has abundant resources and low cost; and belongs to renewable non-grain biomass resource. The method has the advantages of mild reaction condition, no need of noble metal catalysis, simple operation, high yield and large-scale preparation. Benzene ring of the product N-(5-methoxycarbonyl-2-hydroxyphenyl) amino acid ester compounds contains a phenol hydroxyl group (2-site) and a carboxylic acid methyl ester (5-site), which provides a wide space for further derivatization.

Description

technical field [0001] The invention belongs to the field of chemistry and chemical engineering, and relates to a method for N-arylation of amino acid compounds, in particular to a method for preparing N-(5-methoxy Carbonyl-2-hydroxyphenyl) amino acid ester compound method. Background technique [0002] N-arylated amino acid compounds are an important class of organic compounds, and related structure types are widely seen in bioactive molecules and pharmaceutical products. For example: Indolactam-V is an N-aryl amino acid derivative, as an agonist of protein kinase C, in the process of inducing the differentiation of human ES cells into insulin-secreting β cells, it has the ability to induce the differentiation of intestinal ectoderm into Role of pancreatic progenitor cells (Proc. Natl. Acad. Sci. USA, 2009, 106:15768-15773). SB214857 is a GPIIb / IIIa receptor antagonist that can inhibit platelet aggregation and thrombosis (Org. Lett., 2001, 3(16): 2583-2586). JMV1116 is a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C229/64C07C227/18C07C323/58C07C319/20C07C271/28C07C269/06C07D209/20
Inventor 邹永张恩生黄桐堃吕泽良黄琦
Owner GUANGZHOU CHEM CO LTD CHINESE ACADEMY OF SCI
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