Method for one-step synthesis of non-steroidal anti-inflammatory drug diflunisal

A technology of medicine fluorobenzenesalicylic acid and fluorobenzenesalicylic acid, which is applied in the field of catalytic organic synthesis, can solve the problems of environmental hazard, air, humidity sensitivity, etc., and achieves a short reaction time, few by-products, and mild reaction conditions. Effect

Active Publication Date: 2018-10-02
XIANGTAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, ligand-free palladium catalyzes the Suzuki coupling reaction of organoboronic acid and aryl halides. The raw material organoboronic acid is non-toxic, stable and easy to obtain, insensitive to heat, air and humidity, easy to operate, friendly to the environmental process, and the reaction can be performed in aqueous phase. However, most ligand-containing catalysts are harmful to the environment and are sensitive to air and humidity.

Method used

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  • Method for one-step synthesis of non-steroidal anti-inflammatory drug diflunisal
  • Method for one-step synthesis of non-steroidal anti-inflammatory drug diflunisal
  • Method for one-step synthesis of non-steroidal anti-inflammatory drug diflunisal

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1: Ultrasonic Synthesis of Fluorben Salicylic Acid

[0028] Mix 120ml of distilled water and 120ml of N,N-dimethylformamide into the ultrasonic reactor and ultrasonically mix to form solution A, then add 53.2mg of PdCl 2 (0.03mmol) ultrasonically disperse in a cold water bath, add 7.2g 2,4-difluorophenylboronic acid (45mmol), 6.51g 5-bromosalicylic acid (30 mmol) ultrasonically dissolve and disperse in a cold water bath, and finally add 3.36 g K 2 CO 3 (60mmol) ultrasonically dissolved and dispersed, and reacted in an ultrasonic reactor with a temperature of 75°C and an ultrasonic power of 175W for 100min. The flocculent precipitate no longer disappears, then add 2000ml of distilled water to the filtrate, let it stand until the flocculent precipitate of flufenesalic acid is completely precipitated, filter to obtain a white filter cake, dissolve the filter cake with 200ml of ethyl acetate, and wash with deionized water Wash 3 times, take the upper organic ph...

Embodiment 2

[0029] Example 2 Conventional Synthesis of Fluorben Salicylic Acid

[0030]Add 120ml of distilled water and 120ml of N,N-dimethylformamide into a reactor equipped with a condensing device, stir and mix to form a mixed solution A, and then add 53.2mg of PdCl 2 (0.03mmol) ultrasonically dispersed in a cold water bath, then added 7.2 g 2,4-difluorophenylboronic acid (45 mmol), 6.51 g 5-bromosalicylic acid (30 mmol) ultrasonically dissolved and dispersed in a cold water bath, and finally 3.36 g K 2 CO 3 (60mmol) ultrasonically dissolved and dispersed, and mechanically stirred at 75°C for 100min. After the reaction is completed, filter the reacted liquid over the catalyst, add HCl with a concentration of 1mol / L to the filtrate and shake until the precipitated flocculent precipitate no longer disappears, then add 2000ml of distilled water to the filtrate, and let it stand until the fluorobenzene water The flocculent precipitate of sylic acid was completely precipitated, and the wh...

Embodiment 3

[0031] Example 3 The operation steps are the same as in Example 1, but the reaction power is changed to 200W, and the product yield of Fluorben salicylic acid is 89.46%.

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Abstract

Relating to the field of organic synthesis, the invention discloses a method for one-step synthesis of non-steroidal anti-inflammatory drug diflunisal. The method includes: controlling the charging sequence, taking 2, 4-difluorophenylboronic acid and 5-bromosalicylic acid as the raw materials, taking a mixed solution of an aqueous phase and an organic solvent as the solvent, conducting ligand-freepalladium catalysis in the presence of an alkali metal salt, carrying out catalytic reaction under the ultrasonic condition of 70-80DEG C for 90-110min for one-step synthesis of a diflunisal crude product, and further conducting refining to obtain the diflunisal product with yield of 98.37% and purity of 99.89%. The method has the characteristics of green and high efficiency, mild reaction conditions, simple and safe process, and the obtained product has high yield and good purity, and has important industrial prospects.

Description

technical field [0001] The invention belongs to the field of catalytic organic synthesis, and relates to a method for synthesizing a non-steroidal anti-inflammatory drug flubendisalicylic acid in one step. Background technique [0002] Aspirin chemical structure Salicylic acid chemical structure [0003] Compared with aspirin, the introduction of difluorophenyl groups into aspirin strengthens the analgesic and anti-inflammatory effects. The acetyl group of aspirin will acetylate the cyclooxygenase in the human stomach, while the fluorophenyl salicylic acid does not have an acetyl group and does not It will acetylate the cyclooxygenase in the human stomach, so flufenesalic acid is less irritating to the stomach, and at the same time, the incidence of dizziness, tinnitus and edema is low, and it has no effect on the blood system. In addition, it can promote uric acid excretion and enhance renal uric acid clearance rate And lower serum uric aci...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C51/363C07C65/105
CPCC07C51/363C07C65/105
Inventor 吴志民李蓉刘跃进熊迪易洋潘艳娉陆腾飞
Owner XIANGTAN UNIV
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