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Preparation method of glyoxaline formic ether and derivative thereof

A derivative, imidazole technology, applied in the field of pharmaceutical intermediate synthesis, can solve the problems of difficult purification of products, many side reactions, difficult industrial application and the like, and achieves the effects of wide and convenient sources, low production cost and high product yield

Active Publication Date: 2010-04-14
苏州凯达生物医药技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] The purpose of the present invention is to provide a preparation method of imidazole-4-carboxylate and its derivatives, which solves the problem that there are often many side reactions in the preparation of imidazole-4-carboxylate and its derivatives in the prior art, and the product is not easy to purify , it is difficult to carry out industrial application and other problems

Method used

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  • Preparation method of glyoxaline formic ether and derivative thereof
  • Preparation method of glyoxaline formic ether and derivative thereof
  • Preparation method of glyoxaline formic ether and derivative thereof

Examples

Experimental program
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Embodiment 1

[0040] The preparation of embodiment 1 imidazole-4-formic acid ester

[0041] 1) Preparation of glycine ethyl ester

[0042] In glycine (75 grams, 1 mole) and ethanol (450 milliliters), then add catalytic amount of sodium bisulfate, heat, vigorously reflux and stir for 2 to 5 hours; the reaction mixture is cooled to room temperature, suction filtered, and the organic solvent is removed, 98 g (95%) of the desired product were obtained.

[0043] 2) Preparation of N-acetylated glycine ethyl ester

[0044] Glycine ethyl ester (103 g, 1 mole) was dissolved in 600 ml of ethyl acetate, a catalytic amount of DMAP was added, heated, vigorously refluxed and stirred for 2 to 5 hours; the reaction mixture was cooled to room temperature, washed with saturated brine several times, Dry over anhydrous sodium sulfate and remove the organic solvent to obtain 135 g (93%) of the target product.

[0045] 3) Preparation of mercapto-substituted imidazole carboxylic acid compounds

[0046]Sodium ...

Embodiment 2

[0050] The preparation of embodiment 2 imidazole-4-carboxylic acid

[0051] 1) Preparation of glycine methyl ester

[0052] In glycine (75 grams, 1 mole) and methanol (500 milliliters), then pass through hydrogen chloride gas to saturation, heat, and vigorously reflux and stir for 2 to 4 hours; the reaction mixture is cooled to room temperature, suction filtered, and the organic solvent is removed to obtain The target product was 86 grams.

[0053] 2) Preparation of N-acetylated glycine methyl ester

[0054] Glycine methyl ester (89 g, 1 mole) was dissolved in 600 ml of methyl acetate, a catalytic amount of triethylamine was added, heated, and vigorously refluxed and stirred for 2 to 5 hours; the reaction mixture was cooled to room temperature, washed with saturated brine After drying with anhydrous sodium sulfate, the organic solvent was removed to obtain 111 grams of the target product.

[0055] 3) Preparation of mercapto-substituted imidazole carboxylic acid compounds

...

Embodiment 3

[0064] The preparation of embodiment 3 4-hydroxymethylimidazole

[0065] 1) Preparation of glycine ethyl ester

[0066] In glycine (75 g, 1 mole) and ethanol (450 ml), then add a catalytic amount of thionyl chloride, heat, and vigorously reflux and stir for 2 to 5 hours; cool the reaction mixture to room temperature, suction filter, and remove the organic solvent , to obtain 97 g of the target product.

[0067] 2) Preparation of N-acetylated glycine ethyl ester

[0068] Glycine ethyl ester (103 g, 1 mole) was dissolved in 600 ml of ethyl acetate, a catalytic amount of pyridine was added, heated, and vigorously refluxed and stirred for 2 to 5 hours; the reaction mixture was cooled to room temperature, washed with saturated brine several times, Dry over anhydrous sodium sulfate and remove the organic solvent to obtain 120 g (90%) of the target product.

[0069] 3) Preparation of mercapto-substituted imidazole carboxylic acid compound

[0070] Sodium ethylate (102 grams, 1.5 ...

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Abstract

The invention discloses a preparation method of a compound of a formula (I) and a derivative thereof, being characterized by comprising the following steps: (1) obtaining a compound of a formula (II) by esterification reaction of glycine and proper alcohol under the conditions of proper temperature and catalyst; (2) generating a compound of a formula (III) by acylation reaction of the compound of the formula (II); (3) forming a compound of a formula (IV) under acid environment after condensation of the compound of the formula (III) and ethyl formate under alkaline environment; and (4) generating the compound of the formula (I) by oxidation reaction of the compound of the formula (IV) and an oxidant, wherein R1 is selected from alkyl of C1-6 and optional substituted aryl and R2 is selected from C1-4 and optional substituted aryl. The method has easily-obtained materials, simple reaction, moderate and controllable synthesis conditions, high yield of obtained products, little pollution and applicability to industrialized production.

Description

technical field [0001] The invention belongs to the technical field of synthesis of pharmaceutical intermediates, and in particular relates to a preparation method of imidazole formate and derivatives thereof. Background technique [0002] Imidazole (imidazole) is a regular pentagonal planar molecule with good aromaticity and basicity. The nitrogen atoms on the ring are prone to alkylation and acylation reactions. Imidazole is also a good donor and acceptor for forming hydrogen bonds. Therefore, imidazole and its derivatives often have proton-accepting properties, conjugate acid-base properties, complex and coordination properties, etc., and enjoy the reputation of "biocatalyst" and "bioligand". [0003] Imidazole compounds widely exist in alkaloids and amino acids in the human body, and are important structural units in the human body. In the human body, it mainly exists in histidine, which has an important impact on human body functions: for example, in enzymes, the imida...

Claims

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Application Information

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IPC IPC(8): C07D233/90C07D233/64
Inventor 张燕飞陆军韩国彬沈宗旋
Owner 苏州凯达生物医药技术有限公司
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