A kind of preparation method of 2,2-difluoropiperic acid methyl ester

A technology of methyl difluropiperate and difluoropiperic acid is applied in the field of preparation of methyl 2,2-difluoropiperonate, and can solve the problems of easily polluted environment, difficult control of reaction process, complicated purification process, etc. The effect of easy reaction process, high product yield and simple process flow

Active Publication Date: 2017-08-25
辽宁鸿鹄医药化学技术有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Therefore, the technical problem to be solved in the present invention is to overcome the toxic gas involved in the preparation process of methyl 2,2-difluoropiperate in the prior art, the reaction process is not easy to control, the environment is easy to pollute, and the purification process is more loaded down with trivial details, thereby providing A method for preparing methyl 2,2-difluoropiperate with low toxicity to the environment, simple purification in the preparation process, and simple process flow

Method used

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  • A kind of preparation method of 2,2-difluoropiperic acid methyl ester

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Put 660g of DMF, 110g of lithium bromide, and 110g of cuprous cyanide into the dry reaction tank and stir evenly to dissolve the lithium bromide and cuprous cyanide, then add 237g of 5-bromo-2,2-difluoropipercycline, and keep the reaction at 130°C After 5 hours of reaction, cool to 20°C, add 2.7kg of water, and steam distill to obtain a solid product, which is 162g after drying, and the content of 162g of 5-cyano-2,2-difluoropiperone is 99.2%. The yield 88.5%.

[0028] Put 820g of water and 141g of sodium hydroxide into the reaction tank and stir evenly to dissolve the sodium hydroxide, add 162g of 5-cyano-2,2-difluoropipercycline, reflux for 5h, cool to 20°C after the reaction, When it is below 30°C, adjust the pH of the system to 2 with hydrochloric acid with a mass concentration of 30%. The product obtained by suction filtration was 172g after drying, in which the content of 2,2-difluoropiperic acid was 99.6%, and the yield was 96.2%.

[0029] Put 860g of methanol ...

Embodiment 2

[0031] Put 940g of sulfolane, 130g of lithium bromide, and 130g of cuprous cyanide into the dry reaction tank and stir evenly to dissolve the lithium bromide and cuprous cyanide, then add 237g of 5-bromo-2,2-difluoropiperone ring, and keep the reaction at 135°C After 8 hours of reaction, cool to 20°C, add 2.9kg of water, and steam distill to obtain a solid product, which is 167g after drying, and the content of 167g of 5-cyano-2,2-difluoropiperone ring is 99.3%. The yield 91.2%.

[0032] Put 1280g of water and 216g of sodium hydroxide into the reaction tank and stir evenly to dissolve the sodium hydroxide, add 167g of 5-cyano-2,2-difluoropipercycline, reflux for 4 hours, cool to 20°C after the reaction, When it is below 30°C, adjust the pH of the system to 3 with hydrochloric acid with a mass concentration of 30%. The product obtained by suction filtration was 170g after drying, and the content of 2,2-difluoropiperic acid was 99.7%, and the yield was 92.2%.

[0033] Put 1100...

Embodiment 3

[0035] Add 460g of dimethyl sulfoxide, 115g of lithium bromide, and 115g of cuprous cyanide to the dry reaction tank and stir evenly to dissolve lithium bromide and cuprous cyanide, then add 237g of 5-bromo-2,2-difluoropipercycline, Reaction at 125°C for 8 hours. After the reaction, cool to 20°C, add 3.5kg of water, and steam distill to obtain a solid product, which is 164g after drying, and the content of 164g of 5-cyano-2,2-difluoropipercycline is 99.4 %, yield 89.6%.

[0036] Put 1020g of water and 144g of sodium hydroxide into the reaction tank and stir evenly to dissolve the sodium hydroxide, add 164g of 5-cyano-2,2-difluoropipercycline, reflux for 7 hours, cool to 20°C after the reaction, When it is below 30°C, adjust the pH of the system to 2 with hydrochloric acid with a mass concentration of 30%. The product obtained by suction filtration was 171g after drying, the content of 2,2-difluoropiperic acid was 99.4%, and the yield was 94.4%.

[0037] Put 1197g of methanol...

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Abstract

The invention discloses a preparation method of methyl 2,2-difluorobenzo[d][1,3]dioxole-5-carboxylate. The method comprises the steps of performing cyanation reaction to 5-bromo-2,2-difluoro-1,3-benzodioxole and cuprous cyanide, then performing hydrolysis to form acid, and then performing esterification to obtain 2,2-difluorobenzo[d][1,3]dioxole-5-carboxylate. In the preparation method disclosed by the invention, by using 5-bromo-2,2-difluoro-1,3-benzodioxole as a start raw material, performing cyanation by using low-toxicity cuprous cyanide, then performing hydrolysis to form acid and performing methanol reaction esterification to obtain the product, the process flow of the method is simple and the reaction process is easy to control. In the reaction process, the purification of the intermediate product produced in each step does not need a complex purification process, the purification process is simple, the purification yield is high, the entire process flow is simple and high-efficiency, the product yield is high, the cost of the entire flow is low and the preparation method is very suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a preparation method of methyl 2,2-difluoropiperate. Background technique [0002] Methyl 2,2-difluoropiperate is an important intermediate, which is often used in the synthesis of pharmaceutical compounds, pesticide compounds and electronic chemicals. Its methyl ester is a lively substituent group with strong extensibility. [0003] There are two methods for the synthesis of methyl 2,2-difluoropiperate commonly used at present: [0004] Method 1: 3,4-dihydroxynitrobenzene is used as the starting material, first synthesize 5-nitro-2,2-difluoropiperone ring, then reduce and diazotize the bromine, and use carbon dioxide to form an acid under high pressure, and then Ester into 2,2-methyl difluoropiperate. The raw materials of this method are rare, and the operation is cumbersome, which is greatly limited in industrialized large-scale production. [0005] Method 2: Use 5-bromo-2,2...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D317/46
CPCC07D317/46
Inventor 刘民杨银行陈利刘春玉刘伟秦文义
Owner 辽宁鸿鹄医药化学技术有限公司
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