Synthesis method of 2-position aryl substituted benzofuran ring 3-position fluoro

A benzofuran and aryl technology, applied in the field of fluorine organic compounds, can solve the problems of harsh reaction conditions, failure to reflect the application value of organic synthesis, and low yield, and achieve extremely easy operation, good chemical selectivity and functional group Compatibility, the effect of mild reaction conditions

Inactive Publication Date: 2016-08-10
FUDAN UNIV
View PDF1 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] There are very few studies on the synthesis of fluorine-containing compounds at the 3-position of benzofuran. Existing literature reports such as the exchange of F and Br, the use of DAST to obtain difluorine-substituted products, or conversion from alcohols to fluorine, or through metal positioning, and then Methods such as introducing fluorine by fluorinating reagents, but practice has proved that the yields of the methods are very low, the reaction conditions are relatively harsh, and they do not have general applicability, and their application value in organic synthesis has not been reflected so far.

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
  • Synthesis method of 2-position aryl substituted benzofuran ring 3-position fluoro
  • Synthesis method of 2-position aryl substituted benzofuran ring 3-position fluoro
  • Synthesis method of 2-position aryl substituted benzofuran ring 3-position fluoro

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Synthesis of 3-fluoro-2-(4-methoxyphenyl)benzofuran (2a)

[0033] 2-(4-Methoxyphenyl)benzofuran (1a, 112 mg, 0.5 mmol) was dissolved in MeCN (8.0 mL), and SelectFluor (195 mg, 0.55 mmol, 1.1 eq) was added at room temperature (about 25 O c), was added to the solution in water (0.4 ml), then the resulting mixture was stirred at room temperature for 1 h, monitored by TLC (PE:EA = 10:1), once the reaction was complete, the solution in EA (30 ml), and water , washed with brine and dried (Na2SO4), the solvent was removed under reduced pressure, and the residue was used directly in the next step; the residue was dissolved in dry dichloromethane (5 mL), and pyridine (0.41 mL, 5 millimoles, 10 equivalents), and then dropwise added thionyl chloride (0.75 millimoles, 1.5 equivalents, 0.055 ml) solution at this temperature, then the reaction mixture was stirred at room temperature, monitored by TLC overnight, the reaction was complete, and then DCM (10 mL) solution was added, was...

Embodiment 2

[0035] Synthesis of 3-fluoro-2-(2-methoxyphenyl)benzofuran (2b)

[0036] The method is the same as the synthesis of 2a to obtain a colorless oily liquid with a yield of 71%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.70-7.68 (m, 1H), 7.63 (d, J =7.2 Hz, 1H), 7.49 (d, J =8.0 Hz, 1H), 7.44-7.39 (m, 2H), 7.36-7.28 (m, 2H), 7.10 (t, J =7.2 Hz, 1H), 7.03 (d, J =8.0 Hz, 1H), 3.87 (s, 3H) ppm; 13 C NMR (100 MHz, CDCl 3 ) δ 156.75, 151.75 (d, J =8.8 Hz), 144.22 (d, J =255.1 Hz), 136.29 (d, J =24.1 Hz), 130.44, 129.45 (d, J =2.3 Hz), 124.99, 122.88, 120.69 (d, J =20.1 Hz), 120.68, 117.76 (d, J =4.4 Hz), 117.68 (d, J =3.0 Hz), 111.74, 111.57, 55.81 ppm; 19 F NMR (376 MHz, CDCl 3 ) δ -166.06 ppm; IR : (KBr)ν max 2971, 1599, 1495, 1392, 1258, 1026, 744 cm -1; MS (EI) m / z (%): 242 (M+, 100). HRMS calculated value (calcd for) C 15 h 11 FO 2 : 242.0743; Found: 242.0741.

Embodiment 3

[0038] Synthesis of 3-fluoro-2-(3-methoxyphenyl)benzofuran (2c)

[0039] The method is the same as 2a, and a white solid (melting point: 59-61 O C), yield 62%. 1 H NMR (400 MHz, CDCl 3 ) δ 7.61 (d, J =7.2 Hz, 1H), 7.53 (d, J =8.0 Hz, 1H), 7.49-7.45 (m, 2H), 7.40 (t, J =8.0 Hz, 1H), 7.37-7.27 (m, 2H), 6.93-6.90 (m, 1H), 3.90 (s, 3H) ppm; 13 C NMR (100 MHz, CDCl 3 ) δ 159.90, 151.11 (d, J =9.3 Hz), 144.74 (d, J =256.2 Hz), 137.98 (d, J =20.0 Hz), 129.90, 129.84, 125.47, 123.23, 120.63 (d, J =19.3 Hz), 117.66, 117.37 (d, J =6.2 Hz), 114.27, 111.80, 109.79, 55.34 ppm. 19 F NMR (376 MHz, CDCl 3 ) δ -169.48(d, J =1.88 Hz)IR :(KBr)ν max 3066, 1643, 1456, 1345, 1291, 1048, 750cm -1 ; MS (EI) m / z (%): 242 (M+, 100). HRMS calculated value (calcd for) C 15 h 11 FO 2 : 242.0743; Found: 242.0748.

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 fluorine organic compounds, in particular to a synthesis method of 2-position aryl substituted benzofuran ring 3-position fluoro. The method takes 1-chloromethyl-4-fluorodiazabicyclo[2, 2, 2]octane bis(tetrafluoroborate) (Selectfluor) as a fluorinating reagent, in a mixed solvent of acetonitrile and nucleophilic reagent water, a benzofuran compound is efficiently converted into corresponding 3-fluoro-2-ol-2, 3-dihydrobenzofuran, 3-fluoro-2-ol-2, 3-dihydrobenzofuran compound adopts pyridine and thionyl chloride as the dehydrating agent, and can be efficiently converted into a 3-position fluoro 2-position aryl substituted benzofuran compound. The method provided by the invention has the characteristics of mild reaction condition, easy operation, good chemical selectivity and functional group compatibility, and is an effective method for synthesis of 2-position aryl substituted benzofuran ring 3-position fluoro. (reaction formula).

Description

technical field [0001] The invention relates to the technical field of fluoroorganic compounds, in particular to a method for substituting a 2-position aryl group with a 3-position fluorination of a benzofuran ring. Background technique [0002] Studies have reported that heterocyclic structures have made great contributions to the biological activity of drugs. As a large class of heterocyclic structures, benzofuran rings, whether isolated from natural products or chemically synthesized, have shown good Pharmacological activity, especially the 2-aryl substituted benzofuran ring, has a variety of pharmaceutical activities, such as inhibition of cholinesterase activity, inhibition of β-amyloid aggregation, neurotoxicity caused by Aβ, anti-tumor, antibacterial, and antioxidant and anti-HIV biological activity. [0003] Studies have shown that the introduction of fluorine atoms into organic compounds can change the physical, chemical and biological properties of molecules, so f...

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): C07D307/82C07D409/04
Inventor 孙逊王明亮刘希希周昕宇
Owner FUDAN UNIV
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