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Method for preparing 3-difluoromethyl-1-methyl-1H-pyrazol-4-carboxylic acid

A difluoromethyl, C1-C12 technology, applied in the field of preparation of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid, can solve the problem of harsh process conditions, low yield, Industrial scale-up production is difficult and other problems, to achieve the effect of significant technological progress and high productivity

Pending Publication Date: 2018-05-04
SHANGHAI INST OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In view of the above-mentioned technical problems in the prior art, the present invention provides a kind of preparation method of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid, described this 3-difluoro The preparation method of methyl-1-methyl-1H-pyrazole-4-carboxylic acid will solve the method reaction selection of synthetic 3-difluoromethyl-1-methyl-pyrazole-4-carboxylic acid in the prior art Poor performance, low yield; harsh process conditions, difficult to operate; difficult industrial scale-up production; high cost technical problems

Method used

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  • Method for preparing 3-difluoromethyl-1-methyl-1H-pyrazol-4-carboxylic acid

Examples

Experimental program
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Effect test

Embodiment 1

[0039] Preparation of 2-(dimethylaminomethylene)-4,4-difluoro-3-oxo-butyric acid hexyl ester

[0040]

[0041] 1,1,1-trichloro-5,5-difluoro-3-(dimethylaminomethylene)-2,4-pentanedione (10.0mmol, 2.81g) K 2 CO 3 (20.0mmol, 2.76g) and acetonitrile (5ml) mixture was stirred at room temperature for 17h, then cooled to 0°C, concentrated hydrochloric acid was added to adjust pH=1, extracted 3 times with ethyl acetate (10ml), the organic phases were combined, After drying with anhydrous magnesium sulfate and concentrating in vacuo, the target product was obtained quantitatively (HPLC analysis), and the yield was 100%.

Embodiment 2

[0043] Preparation of 3-(difluoromethyl)-1-methyl-1H-pyrrolyl-4-carboxylic acid hexyl ester

[0044]

[0045] An aqueous solution of methylhydrazine (40%, 12mmol, 1.38g), 48% NaOH (2mmol, 167mg) and dichloromethane (5ml) were mixed and cooled to -15°C, and added to 2-(dimethyl Aminomethylene)-4,4-difluoro-3-oxo-butyric acid hexyl ester (10mmol, 2.77g) in dichloromethane solution (5ml). The reaction was continued at the same temperature for 4 h, then neutralized to neutral by adding 2N HCl, the temperature was raised to room temperature, extracted three times with dichloromethane, the organic phase was combined, washed with water, dried with anhydrous magnesium sulfate, concentrated under reduced pressure . The target product was purified by column chromatography with a yield of 85%.

Embodiment 3

[0047] Preparation of 3-Difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid

[0048]

[0049] 3-(Difluoromethyl)-1-methyl-1H-pyrrolyl-4-carboxylic acid hexyl ester (5mmol, 1.30g) and 10% NaOH aqueous solution (8mmol, 3.10g) were stirred at 60°C for 2h. The reaction Cool to room temperature, and adjust pH to 1 by adding concentrated hydrochloric acid. The precipitate was filtered, washed with cyclohexane, and dried in vacuo to obtain pure 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid in 95% yield.

[0050] The above examples show that, according to the preparation method provided by the present invention, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid can be generated with high selectivity. The whole implementation process is simple and easy to operate, can meet technical and economic requirements, and is friendly to the environment.

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Abstract

The invention provides a method for preparing 3-difluoromethyl-1-methyl-1H-pyrazol-4-carboxylic acid. The method comprises the following steps: under the action of an alkali, enabling 1,1,1-trichlorine-3-(substituted amino methylene)-5,5-difluoro-2,4-pentanedione to react with n-alcohol to generate 2-(substituted amino methylene)-4,4-difluoro-3-oxo-butyrate, further reacting with a methylhydrazinesolution to generate 3-difluoromethyl-1-methyl-1H-pyrazolyl-4-formate, and finally performing hydrolysis under an alkali condition, thereby obtaining the 3-difluoromethyl-1-methyl-1H-pyrazol-4-carboxylic acid. The invention provides a novel economic method, and 2-(substituted amino methylene)-4,4-difluoro-3-oxo-butyrate which is high in yield and high in purity is firstly prepared, and is furtherhighly selectively converted into a target product, namely 3-difluoromethyl-1-methyl-1H-pyrazol-4-carboxylic acid.

Description

technical field [0001] The invention belongs to the field of chemical industry, and specifically relates to a preparation method of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid. Background technique [0002] Fluorine-containing amides and pyrazoles have the advantages of high activity, low residue, environmental friendliness, good safety, and low price, and are widely developed and utilized in the fields of medicine and pesticides. People have successively developed a number of heavyweight fungicidal products, such as Bixafen, Fluxapyroxad and Isopyrazam, etc., which will have quite broad market prospects in the next ten years. Among them, 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid is a key intermediate for the synthesis of several new fluorine-containing pyrazole fungicides, and has been mass-produced at home and abroad. Since Japanese Patents JP2000128763 and JP20002012166 reported the synthesis method of this type of compound in 2000, there have...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/14
CPCC07D231/14
Inventor 刘慧敏王伟刘清雷
Owner SHANGHAI INST OF TECH
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