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Method for preparing acrylic nitrile derivates

A derivative, acrylonitrile technology, applied in the field of preparation of acrylonitrile derivatives, can solve the problems of cumbersome preparation of DMFA and increased cost, and achieve the effects of low cost, mild reaction conditions, and simplified reaction steps

Active Publication Date: 2009-06-17
ZHEJIANG GUOBANG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0024] There is also the shortcoming of making β-keto ester earlier in the above-mentioned route, and the cost increases
At the same time, DMFA is needed, and the preparation of DMFA is tedious

Method used

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  • Method for preparing acrylic nitrile derivates
  • Method for preparing acrylic nitrile derivates
  • Method for preparing acrylic nitrile derivates

Examples

Experimental program
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Effect test

preparation example Construction

[0042] The preparation method of acrylonitrile derivative of the present invention, its reaction mechanism is as follows:

[0043]

[0044] In each of the above molecular structural formulas: R is C 1 ~C 6 Any of the alkyl groups; X 1 、X 2 、X 3 、X 4 Both are halogen, hydrogen, amino or nitro; X 5 Halogen; Halogen is fluorine, chlorine; metal cation M is Na + or K + . Amination reagent RNH 2 Including cyclopropylamine, L-aminopropanol, ethylamine, and p-fluoroaniline, which have the following structure:

[0045]

[0046] Imine salt (Methoxymethylen) dimethylammonium-methylsulfat) can be obtained by reacting N,N-dimethylformamide (DMF) with dimethyl sulfate.

[0047] The solution of the aminoacrylonitrile derivative obtained by the above reaction can be post-treated according to the prior art, that is, the finished product of the acrylonitrile derivative can be obtained through organic solvent crystallization. The cyclization reaction can be directly carried out...

Embodiment 1

[0049] Embodiment 1: The preparation of 3-cyclopropylamino-2-(2,4-dichloro-5-fluorobenzoyl)acrylonitrile, the following steps are carried out in sequence:

[0050] 1. Preparation of 3-N, N-dimethylaminoacrylonitrile: 28.84g (0.234mol) potassium cyanoacetate and 160ml toluene were thrown into a 500ml four-necked flask, and 67.53g (0.339g) was added dropwise at a temperature of about 25°C. III, the dropwise addition is completed in about 2 hours, and the room temperature is kept overnight, and 116ml of 5% sodium hydroxide aqueous solution is added to the feed liquid, stirred for 5 minutes, and separated into layers, and the obtained toluene layer is dried using anhydrous sodium sulfate to obtain The toluene solution of dimethylaminoacrylonitrile contained 13.50 g (0.14 mol) of dimethylaminoacrylonitrile (60% conversion rate) and was directly used in the following steps without purification.

[0051] 2. Preparation of 3-N,N-dimethylamino-2-(2,4-dichloro-5-fluorobenzoyl)-acrylonit...

Embodiment 2

[0053] Example 2: The preparation of 3-(2-S-1-hydroxypropylamine)-2-(2,3,4,5,6-pentafluorobenzoyl)acrylonitrile, the following steps are carried out in sequence:

[0054] 1. Preparation of 3-N, N-dimethylaminoacrylonitrile: Throw 19.32g (0.157mol) potassium cyanoacetate and 150ml methylene chloride in a 500ml four-necked flask, and add 59.21g ( 0.298mol) III, about 4 hours after the dropwise addition, keep warm at about 40°C for 5 hours, add 100ml of 5% sodium hydroxide aqueous solution to the feed liquid, stir for 5 minutes, separate layers, and use anhydrous sulfuric acid for the obtained toluene layer After drying with sodium, a dichloromethane solution containing dimethylaminoacrylonitrile was obtained, which contained 10.00 g (0.104 mol) of dimethylaminoacrylonitrile (66% conversion) and was used directly in the following steps without purification.

[0055] 2. Preparation of 3-N,N-dimethylamino-2-(2,3,4,5,6-pentafluorobenzoyl)-acrylonitrile: inject 10.00g (0.104mol) into...

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Abstract

The invention provides a method for preparing an acrylonitrile derivative, which belongs to the technical field of preparation of fluoroquinolones medical intermediates and other compounds. The method comprises the following steps: A, using cyano-acetate and imine salts as raw materials, and gradually dripping the imine salts into an organic solvent of the cyano-acetate to react for 0.5 to 80 hours at a temperature of between 0 and 80 DEG C, so as to obtain a solution of dimethyl amino acrylonitrile; B, gradually adding acyl chloride as a raw material to the organic solvent of the dimethyl amino acrylonitrile solution obtained in the step A to react for 0.5 to 40 hours at a temperature of between 10 below zero and 100 DEG C, so as to obtain a solution of 3-dimethylamino-2-aryl acrylonitrile; and C, dripping an aminate reagent into the organic solvent of the 3-dimethylamino-2-aryl acrylonitrile solution obtained in the step B to react for 0.5 to 40 hours at a temperature of between 20 below zero and 80 DEG C, so as to obtain a solution of the acrylonitrile derivative. The process has the advantages of reasonable design and high yield.

Description

technical field [0001] The invention relates to a preparation method of acrylonitrile derivatives, belonging to the technical field of preparation of fluoroquinolone drug intermediates and other compounds. Background technique [0002] Fluoroquinolones have been widely used as antibiotics, and the synthetic methods of their key intermediate acrylonitrile derivatives (molecular structural formula is I) have multiple reports. Taking the synthesis of cyclopropanecarboxylic acid (molecular formula A), the main ring compound of ciprofloxacin, one of the fluoroquinolones, as an example, the synthesis method of cyclopropanecarboxylic acid (A) will be introduced. [0003] [0004] In molecular structure formula I: R is C 1 ~C 6 Any of the alkyl groups; X 1 、X 2 、X 3 、X 4 Both are halogen, hydrogen, amino or nitro; X 5 for halogen. [0005] The synthetic routes suitable for industrialized production are mainly divided into two types according to different starting material...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C255/42C07C253/30
Inventor 刘聪潘峰李睿婷侯仲轲廖仕学田利焕
Owner ZHEJIANG GUOBANG PHARMA