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

A technology of ester compounds and hydroxyphenyl, applied in the field of preparation of 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, sustainable The effect of preparation

Active Publication Date: 2012-12-12
GUANGZHOU CHEM CO LTD CHINESE ACADEMY OF SCI
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  • Summary
  • 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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

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

[0032] Take 3-dehydroshikimate methyl ester (0.93g, 5.0mmol), anhydrous aluminum trichloride (0.03g, 0.25mmol), 10g 3A molecular sieve in the reaction flask, and put 20ml of L-alanine methyl ester in ethanol solution ( 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 hours, followed by TLC. After the reaction, it was cooled, filtered, the solvent was removed by rotary evaporation, column chromatography, eluted with ethyl acetate-petroleum ether, concentrated to remove the solvent to obtain a pale yellow oily liquid (([α] 25 / D = -63.79, c=0.59 (anhydrous ethanol) 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 2 =1.7...

Embodiment 2

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

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

[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=8.00Hz,1H),5.30(s,1H),3.96(s,2H),...

Embodiment 3

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

[0040] Take 3-dehydroshikimate methyl ester (0.93g, 5.0mmol), acetic acid (14.30μl, 0.25mmol), 10g3A molecular sieve in the reaction flask, add 20ml of L-isoleucine methyl ester in 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 hours, followed by TLC. After the reaction, it was cooled, filtered, the solvent was removed by rotary evaporation, column chromatography, eluted with ethyl acetate-petroleum ether, and recrystallized to obtain a pale yellow solid (([α] 25 / D = -83.80, c=0.28 (anhydrous ethanol) 1.18g, yield: 80%. m.p.109~111℃.

[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 =8.18,J 2 =1.86Hz,1H), 7.03(d,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) by using methyl 3-dehydroshikimate as the N-arylation reagent 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 structural types are widely found in biologically active molecules and pharmaceutical products. For example: Indolactam-V is a kind of N-aryl amino acid derivatives, as an agonist of protein kinase C, in the process of inducing the differentiation of human ES cells into insulin-secreting β cells, it can induce the differentiation of intestinal ectoderm into The role of pancreatic progenitor cells (Proc. Natl. Acad. Sci. USA, 2009, 106: 15768-15773). SB214857 is a GPIIb / IIIa receptor antagonist, which can inhibit platelet aggregat...

Claims

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Application Information

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Patent Type & Authority Applications(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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