Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of tiaprofenic acid

A technology of tiaprofenic acid and thiophene, which is applied in the field of preparation of non-steroidal anti-inflammatory drug tiaprofenic acid, can solve the problems of difficult storage of tiaprofenic acid reaction raw materials, harsh reaction conditions, large environmental pollution, etc., and achieves convenient Industrial production, stable reaction conditions, and simple post-processing effects

Inactive Publication Date: 2012-09-12
SOUTHEAST UNIV
View PDF4 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0018]Technical problem: The present invention is aimed at preparing tiaprofen acid, and the reaction raw materials are difficult to preserve, or the reaction yield is low, or the environmental pollution is large, or the reaction conditions are harsh, or Due to the high defects of reaction cost, a new preparation method of tiaprofen acid is proposed

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
  • Preparation method of tiaprofenic acid
  • Preparation method of tiaprofenic acid
  • Preparation method of tiaprofenic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] The synthesis of embodiment 1 2-propionyl thiophene

[0042]Add 32mL (0.4mol) of thiophene, 64mL (0.5mol) of propionic anhydride, 4mL of phosphoric acid and 0.8g (6mmol) of phosphorus pentoxide into a 250mL eggplant-shaped bottle at one time, and heat the oil bath to reflux at 95-100°C. After 20 minutes of reaction, the clarified system began to darken. With the prolongation of the reaction time, the color of the system gradually turned dark brown, and "white smoke" was continuously generated in the bottle. Stop the reaction after 6h-8h, cool the system to room temperature, add 100mL water and stir for 20min, extract with 3x50mL dichloromethane, combine the organic layer; stir the organic layer with 15% NaOH solution 100mL at room temperature for 1h until the upper aqueous solution of the system becomes alkaline, Then wash with 4x50mL saturated saline. Anhydrous sodium sulfate was dried overnight, filtered, and the solvent was distilled off under reduced pressure to ob...

Embodiment 2

[0043] Example 2 Synthesis of α-bromo-2-propionylthiophene

[0044] Add 14g (0.1mol) of 2-propionylthiophene and 60mL of refined ether solvent into a dry 250mL eggplant-shaped bottle. The temperature of the system was lowered to 0°C in an ice-salt bath, and 1.4 g (0.01 mol) of anhydrous aluminum trichloride catalyst was added. Add 8g (0.1mol) of bromine dropwise under stirring. When adding bromine dropwise, add 2 drops of bromine first, and then quickly add the remaining bromine dropwise after the color in the system fades away. At this time, the bromine added dropwise rapidly became colorless, and the generated hydrogen bromide was absorbed with 10% sodium hydroxide. After 10 minutes of dripping, the system is light red. The reaction was continued at this temperature for 30 min. The reaction was stopped, and the system was poured into a 200mL ice-water bath. At this time, the system changed from light red to light yellow, and stirred for several minutes. Wash with saturat...

Embodiment 3

[0046] Example 3 Synthesis of 2-(1-bromoethyl)-2-(2-methylthiophene)-1,3-dioxane

[0047] Add 44.0g (0.2mol) of α-bromo-2-propionylthiophene, 240mL of toluene and 4.4g of p-toluenesulfonic acid to a 500mL dry three-necked flask, heat up to 140°C in an oil bath, and vigorously reflux. After the temperature stabilized, start adding 2 equivalents of ethylene glycol. The temperature was refluxed for 12h, and the reaction was stopped. After the system was cooled to room temperature, it was washed with 3x40mL saturated brine. The upper layer was dried, filtered, and the solvent was evaporated to obtain 52.4 g of a light yellow oil, and the structure of the product was: , yield 99.3%, HPLC>99%.

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 provides a preparation method of tiaprofenic acid. The method comprises the following steps of: reacting thiofuran serving as a starting raw material with propionic andydride to obtain 2-propionyl thiofuran; reacting the 2-propionyl thiofuran with bromine to obtain alpha bromo on a thiophene ring branch chain; refluxing the obtained bromo compound and ethylene glycol to obtain a bromo-ketal product; rearranging the bromo-ketal product under the action of cuprous oxide serving as a catalyst; performing a Friedel-Crafts reaction on a rearrangement product and benzoyl chloride; and hydrolyzing and acidifying to obtain tiaprofenic acid serving as a target product. The method has stable reaction conditions and high yield; a crude product obtained after reacting has high purity, is easy for purifying and operating, and is low in cost; and used reagents are conventional reagents, so that post-treatment is easy, and convenience is brought to industrial production.

Description

technical field [0001] The invention belongs to the field of medicine preparation, and in particular relates to a preparation method of non-steroidal anti-inflammatory drug tiaprofen acid. Background technique [0002] Tiaprofen acid (structural formula shown below) is also known as tiaprofenic acid, phenylthiopropionic acid, isothirone ibuprofen, and its chemical name is 5-benzoyl-α-methyl-2-thiopheneacetic acid. It is a derivative of thienylpropionic acid, a new type of non-steroidal anti-inflammatory drug, developed by the French Roussol-Uclaf Central Research Institute. According to the chemical structure classification, it belongs to propionic acid non-steroidal anti-inflammatory drugs. The medicine has good oral property, can be rapidly absorbed in the gastrointestinal tract, has antipyretic, analgesic and anti-inflammatory effects, can reduce swelling, relieve joint stiffness, relieve pain, and improve joint movement. The mechanism of action is to inhibit the synthe...

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): C07D333/24
Inventor 吉民蔡进李锐黄双
Owner SOUTHEAST UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com