Method for preparing benzisoxazole in one pot based on 2-hydroxyacetophenone oxime and derivatives thereof

A technology of hydroxyacetophenone oxime and benzisoxazole, which is applied in the field of medicinal chemistry, can solve problems such as limiting practical application value, and achieve the effects of high product yield, short synthesis steps, and easy-to-obtain raw material sources

Active Publication Date: 2017-03-29
HUAWEI TEHCHNOLOGIES CO LTD
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this method can obtain benzoisoxazole compounds in higher yields, the raw materials used in t

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing benzisoxazole in one pot based on 2-hydroxyacetophenone oxime and derivatives thereof
  • Method for preparing benzisoxazole in one pot based on 2-hydroxyacetophenone oxime and derivatives thereof
  • Method for preparing benzisoxazole in one pot based on 2-hydroxyacetophenone oxime and derivatives thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0018] Example 1: 3-Methylbenzisoxazole

[0019]

[0020] Weigh 0.304g (2mmol) of 2-hydroxyacetophenone oxime, 0.457g (3mmol) of sodium difluorochloroacetate, and 0.417g (3mmol) of potassium carbonate into a 50mL three-necked flask, and add 2mL of N,N-dimethylethyl The amide was used as the solvent, stirred evenly by magnetic force, put it into a microwave catalytic synthesizer, manually set the parameters (microwave power 300W, temperature 85°C, microwave time 35min), and carried out microwave reaction. After the reaction was completed, it was cooled to room temperature, 10 mL of deionized water and 10 mL of ethyl acetate were added to the reaction system for extraction, and the organic phase was separated and washed three times with 10 mL of deionized water. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated in vacuo to obtain a crude product. The crude product was purified by silica gel column chromatography (ethyl ace...

example 2

[0021] Example 2: 3,5-Dimethylbenzisoxazole

[0022]

[0023] Weigh respectively 0.332g (2mmol) of 5-methoxy-2-hydroxyacetophenone oxime, 0.609g (2mmol) of potassium difluorobromoacetate, and 0.424g (4mmol) of sodium carbonate in a 50mL three-necked flask, and add 4mL of dimethyl Sulfoxide is used as a solvent, and it is heated to 100°C for 240 minutes. After the reaction was completed, it was cooled to room temperature, 10 mL of deionized water and 10 mL of ethyl acetate were added to the reaction system for extraction, and the organic phase was separated and washed three times with 10 mL of deionized water. The organic phase was dried over anhydrous magnesium sulfate, filtered, and the organic phase was removed by vacuum rotary evaporation to obtain a crude product. The crude product was purified by silica gel column chromatography (ethyl acetate / petroleum ether=1:20) to obtain 0.133g of 3,5-dimethylbenzisoxazole with a yield of 45%. 1 HNMR (400MHz, CDCl 3 )δ7.30~7.40 ...

example 3

[0024] Example 3: 5-Chloro-3-methylbenzisoxazole

[0025]

[0026] Synthesized in a method similar to Example 1, raw material is 0.373g (2mmol) 5-chloro-2-hydroxyacetophenone oxime, promotor is 0.812g (4mmol) ethyl bromodifluoroacetate, alkali is 0.326g (1mmol) carbonic acid Cesium, the solvent is 1mL N-methylpyrrolidone, and the power is 200W, the temperature is 70°C, microwave reaction is 60min, and 0.125g of 5-chloro-3-methylbenzisoxazole is obtained, and the yield is 37%. 1 HNMR (400MHz, CDCl 3 )δ7.60(s,1H),7.48(s,2H),2.57(s,3H).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to the technical field of medicinal chemistry and in particular discloses a method for preparing benzisoxazole in one pot based on 2-hydroxyacetophenone oxime and derivatives thereof. The preparation method is as follows: under microwave or oil bath heating conditions, in an organic solvent, one-pot inversion is carried out on 2-hydroxyacetophenone oxime and derivatives thereof to form benzisoxazole compounds by utilizing a fluorine-containing accelerator and alkali. The method for synthesizing benzisoxazole has the advantages that raw materials are rich in source and easy to get, synthetic steps are short, the operation is simple and convenient, the product yield is high, and the highest yield is 93%. A benzisoxazole structure exists in multiple drug molecules, so that the novel one-pot synthesis method disclosed by the invention has potential practical values.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, and specifically discloses a one-pot method for preparing benzisoxazole based on 2-hydroxyacetophenone oxime and derivatives thereof. Background technique [0002] Benzisoxazole is a class of benzoheterocyclic compounds containing adjacent oxygen and nitrogen atoms, which have high biological activity and pharmaceutical properties. Benzisoxazole exists in a large amount in drugs with stability (Journal of Medicinal Chemistry, 1995, 38, 1119), antitumor (Journal of Medicinal Chemistry, 2008, 51, 373), anticonvulsant (Drug Metabolism & Disposition, 1990, 18, 888), antimicrobial ( Bioorganic & Medicinal Chemistry, 2005, 13, 2623), antithrombotic (Cheminform, 1994, 25, 75) and inhibition of cholinesterase (Journal of Physical Organic Chemistry, 2005, 18, 773). [0003] The traditional synthesis method of benzisoxazole (European Journal of Medicinal Chemistry 2014, 84, 42) needs to go thr...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D261/20
CPCC07D261/20
Inventor 华明清牟方友张岐刘威旱王韬
Owner HUAWEI TEHCHNOLOGIES CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap