Method for synthesis of flurbiprofen

A technology of flurbiprofen and fluorobiphenyl, which is applied in the field of compound synthesis, can solve the problems of complex operation and long preparation route, and achieve the effect of wide source of raw materials, low cost and easy operation

Inactive Publication Date: 2011-02-16
UNIV OF SCI & TECH OF CHINA
View PDF5 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These methods have long preparation routes and complicated operations

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 synthesis of flurbiprofen
  • Method for synthesis of flurbiprofen
  • Method for synthesis of flurbiprofen

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] (1) Preparation of 2-(2-fluorobiphenyl-4-yl)propionitrile

[0078] In an oven-dried 100 mL Schlenk flask equipped with a magnet, add dipolyallylpalladium chloride (0.0146 g, 0.040 mmol), 9,9-dimethyl-4,5-bis(di tert-butylphosphino)xanthene (0.0693 g, 0.120 mmol), 4-bromo-2-fluorobiphenyl (10.04 g, 40 mmol) and potassium 2-cyanopropionate (6.58 g, 48 mmol). The lid is coated with a vacuum grease grinding plug, connected to the Schrank vacuum line, the air in the container is drained and filled with nitrogen, repeat 3 times, and 40mL of mesitylene is added under the reverse flow of nitrogen. After the addition, cover with a stopper, put it into a 140°C oil pan after clamping, and stir for 20 hours. After the reaction was completed, it was directly separated by chromatographic column to obtain white crystals with a yield of 95%.

[0079] (2) Preparation of 2-(2-fluorobiphenyl-4-yl)propionic acid

[0080] In a clean 100mL round bottom flask equipped with a magnet, add 2-...

Embodiment 2

[0083] (1) Preparation of 2-(2-fluorobiphenyl-4-yl)acetonitrile

[0084] Add palladium chloride (0.0071 g, 0.040 mmol), 2-bicyclohexylphosphine-2′, 6′-dimethoxybiphenyl (0.0493 g, 0.120mmol), 4-chloro-2-fluorobiphenyl (8.27g, 40mmol) and sodium cyanoacetate (5.14g, 48mmol). The lid is coated with a vacuum grease grinding plug, connected to the Schrank vacuum line, the air in the container is drained and filled with nitrogen, repeat 3 times, and 40mL of mesitylene is added under the reverse flow of nitrogen. After the addition, cover with a stopper, put it into a 140°C oil pan after clamping, and stir for 20 hours. After the reaction was completed, it was directly separated by chromatographic column to obtain white crystals with a yield of 96%.

[0085] (2) Preparation of 2-(2-fluorobiphenyl-4-yl)propionitrile

[0086] In a 150 ml round bottom flask equipped with a magnet was added 2-(2-fluorobiphenyl-4-yl)acetonitrile (7.60 g, 36 mmol), NaH (0.86 g, 36 mmol) and 80 mL of DM...

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 method for the synthesis of flurbiprofen, which comprises the step that: 4-halo-2-fluorobiphenyl and cyanoacetic acid salt derivative are dissolved in solvent to be subjected to decarboxylation coupled reaction, methylation and hydrolysis under the action of palladium catalyst and organophosphorus ligand, in order to synthesize the target product within three steps; the method has the advantages of great simplicity and convenience, easy operation, wide source of raw materials, low cost, only the generation of inorganic salt and carbon dioxide in the synthesis process,good safety, environmental protection, consistency with the requirement of green chemistry and superior suitability for industrial production.

Description

technical field [0001] The invention relates to the field of compound synthesis, in particular to a method for synthesizing flurbiprofen. Background technique [0002] The chemical name of flurbiprofen is 2-(2-fluorobiphenyl-4-yl)propionic acid. Its chemical formula is: [0003] [0004] Flurbiprofen (Flurbiprofen) is a non-steroidal anti-inflammatory analgesic developed by British Boots Company. The drug was launched in the UK in 1976 and has been included in the pharmacopoeias of the UK and the US. It is one of the excellent non-steroidal anti-inflammatory analgesics and is mainly used for the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. , traumatic pain and other pain. [0005] The existing flurbiprofen synthesis methods mainly include Chinese Journal of Pharmaceutical Industry 1990, 21 (6), 285, Chinese Journal of Pharmaceutical Industry 1991, 22 (1), 2, European Patent 0032620, US Patent 3959364 and Chinese Patent 200910031714.8. ...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07C51/08C07C57/58
Inventor 尚睿黄铮傅尧刘磊
Owner UNIV OF SCI & TECH OF CHINA
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