Preparation method of 5-methylpyrazinyl-2-carboxylic acid

A technology of methylpyrazine and dimethylpyrazine, which is applied in the field of preparation of pharmaceutical intermediates, can solve the problems of corrosion, difficult removal, and corrosion of reaction vessels, and achieves the advantages of reducing the degree of corrosion, reducing equipment costs, and improving safety. Effect

CN102924389AInactive Publication Date: 2013-02-13BEIJING UNIV OF TECH
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
Publication Date
2013-02-13
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention relates to a preparation method of 5-methylpyrazinyl-2-carboxylic acid, which comprises the following steps: by using methanol or ethanol as a solvent and 1-150 ppm mononuclear metalloporphyrin disclosed as Formula (I) or Formula (II) as a catalyst, introducing 0.5-2.5 MPa oxygen into a 0.5-5.0 mol / L sodium hydroxide solution, and reacting at 60-120 DEG C for 4-12 hours to obtain the 5-methylpyrazinyl-2-carboxylic acid. By using the metalloporphyrin as the catalyst and the ethanol alkali solution as the solvent, the method has the advantages of small catalyst consumption, no pollution and green solvent, greatly lowers the corrosion of potassium bromide and acid to reaction equipment, and enhances the experimental operation safety.
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Description

technical field

[0001] The invention relates to a preparation method of 5-methylpyrazine-2-carboxylic acid, belonging to the technical field of preparation of pharmaceutical intermediates. Background technique

[0002] 5-Methylpyrazine-2-carboxylic acid is a nitrogen-containing heterocyclic compound. It has good biological activity and is an important pharmaceutical intermediate. It is mainly used in the synthesis of the second-generation sulfonylurea hypoglycemic drug Glipira Zine and a new generation of long-acting hypolipidemic drug acipimox. At present, the synthesis methods of 5-methylpyrazine-2-carboxylic acid are divided into three categories according to the types of chemical reactions: microbial synthesis, electrochemical oxidation, and chemical synthesis.

[0003] Chinese patent CN 101863845A (disclosure date: October 20, 2010) discloses a preparation method of 5-methylpyrazine-2-carboxylic acid. The method uses 2,5-dimethylpyrazine as raw material, cobalt acetat...

Examples

Embodiment 1

[0027] In a 200mL autoclave, add 2.4g sodium hydroxide, 1.98g 2,5-dimethylpyrazine, 30mL ethanol, 100ppm tetrakis-(4-chlorophenyl) iron porphyrin (formula (I) structure R 11 =R 12 = H, R 13 = Cl, M 1 =Fe), feed 1.5MPa of oxygen, and react at 100°C for 10 hours. After the reaction, dilute the reaction solution with a solvent, take a certain amount of the reaction solution in a 10mL volumetric flask, add dilute hydrochloric acid to acidify, constant volume, and filter to obtain 5-methylpyrazine-2-carboxylic acid. According to high performance liquid chromatography analysis, the conversion rate of 2,5-dimethylpyrazine was 25.6%, and the yield of 5-methylpyrazine-2-carboxylic acid was 21.4%.

Embodiment 2

[0029] In a 200mL autoclave, add 0.6g sodium hydroxide, 1.98g 2,5-dimethylpyrazine, 30mL ethanol, 80ppm tetrakis-(4-chlorophenyl) iron porphyrin (formula (I) structure R 11 =R 12 = H, R 13 = Cl, M 1 =Fe), feed 2.0MPa of oxygen, and react at 100°C for 11 hours. After the reaction, dilute the reaction solution with a solvent, take a certain amount of the reaction solution in a 10mL volumetric flask, add dilute hydrochloric acid to acidify, constant volume, and filter to obtain 5-methylpyrazine-2-carboxylic acid. After HPLC analysis, the conversion rate of 2,5-dimethylpyrazine was 7.8%, and the yield of 5-methylpyrazine-2-carboxylic acid was 5.6%.

Embodiment 3

[0031] In a 200mL autoclave, add 3.6g sodium hydroxide, 1.98g 2,5-dimethylpyrazine, 30mL ethanol, 100ppm tetrakis-(4-chlorophenyl) manganese porphyrin (formula (I) R 11 =R 12 = H, R 13 = Cl, M 1 =Mn), feed 1.5MPa of oxygen, and react at 100°C for 8 hours. The aftertreatment steps are the same as in Example 1 to obtain 5-methylpyrazine-2-carboxylic acid. According to high performance liquid chromatography analysis, the conversion rate of 2,5-dimethylpyrazine was 28.7%, and the yield of 5-methylpyrazine-2-carboxylic acid was 24.3%.