Synthetic method of fluorine-containing alkyl substituted 2,3-dihydrocoumarone derivatives and indole derivatives

A technology of furan derivatives and indole derivatives, which is applied in the direction of organic chemistry and the like, achieves the effects of simple operation, mild reaction conditions and good industrial application prospects

Active Publication Date: 2017-04-19
SOUTH CHINA UNIV OF TECH
View PDF3 Cites 17 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However when building C sp3 -CF 2 There are quite few reports on key (a) K.Uneyama, T.Yanagiguchi, H.Asai, Tetra.Lett.1997, 38, 7163; b) Z.Ye, K.E.Gettys, X.Shen, M.Dai, Org .Lett.2015, 17, 6074; c) P.Xu, K.Hu, Z.Gu, Y.Cheng, C.Zhu, Chem.Commun., 2015, 51, 7222;), especially one-step efficient simultaneous construction C sp3 -CF 2 bonds and C-X bonds are less reported (Z. Zhang, X. Tang, C. S. Thomoson, W. R. D. Jr, Org. Lett. 2015, 17, 3528)

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
  • Synthetic method of fluorine-containing alkyl substituted 2,3-dihydrocoumarone derivatives and indole derivatives
  • Synthetic method of fluorine-containing alkyl substituted 2,3-dihydrocoumarone derivatives and indole derivatives
  • Synthetic method of fluorine-containing alkyl substituted 2,3-dihydrocoumarone derivatives and indole derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] In a 25 ml sealed tube reaction flask, add 0.15 mmol 2-allylphenol, 0.3 mmol ethyl iododifluoroacetate, 0.0075 mmol tetrakistriphenylphosphine palladium, 0.015 mmol 1,1'-bis (Diphenylphosphino)ferrocene, 0.3 mmol of cesium carbonate, 2 ml of toluene, the reaction system was stirred at 90° C. for 19 hours, stopped heating and stirring, and cooled to room temperature. Ethyl acetate extracted the reaction solution, decompressed rotary evaporation to remove the solvent, and then separated and purified by column chromatography to obtain the target product. The column chromatography eluent used was a volume ratio of 100:1 petroleum ether: ethyl acetate mixed solvent , the yield was 71%.

[0036] The proton nuclear magnetic spectrum, the fluorine spectrum and the carbon spectrum of the product obtained in this embodiment are respectively as follows figure 1 , figure 2 with image 3 As shown, the structural characterization data are as follows:

[0037] 1 H NMR (400MHz, CDC...

Embodiment 2

[0041] In a 25 ml sealed tube reaction flask, add 0.15 mmol 4-methyl 2-allylphenol, 0.3 mmol ethyl iododifluoroacetate, 0.0075 mmol tetrakistriphenylphosphine palladium, 0.015 mmol bis( Diphenylphosphorus)-1,1'-binaphthyl, 0.3 mmol potassium carbonate, 2 ml 1,4-dioxane, the reaction system was stirred at 90°C for 20 hours, stopped heating and stirring, and cooled to room temperature. Ethyl acetate extracted the reaction solution, decompressed rotary evaporation to remove solvent, and then separated and purified by column chromatography to obtain the target product. The column chromatography eluent used was a volume ratio of 100:1 petroleum ether: ethyl acetate mixed solvent , the yield was 60%.

[0042] The structural characterization data of the product obtained in this embodiment are as follows:

[0043] 1 H NMR (400MHz, CDCl 3 )δ6.97(s,1H),6.90(d,J=8.1Hz,1H),6.60(d,J=8.1Hz,1H),5.02-4.95(m,1H),4.39-4.31(m,2H ), 3.36(dd, J=9.0Hz, J=15.6Hz, 1H), 2.89(dd, J=7.0Hz, J=15.6Hz,...

Embodiment 3

[0047] In a 25 ml sealed tube reaction flask, add 0.15 mmol 4-bromo-2-allylphenol, 0.3 mmol ethyl iododifluoroacetate, 0.0075 mmol dichlorodiacetonitrile palladium, 0.015 mmol 1,1 '-bis(diphenylphosphino)ferrocene, 0.3 mmol potassium acetate, 2 ml 1,4-dioxane, the reaction system was stirred and reacted at 80°C for 20 hours, stopped heating and stirring, and cooled to room temperature. Ethyl acetate extracted the reaction solution, decompressed rotary evaporation to remove the solvent, and then separated and purified by column chromatography to obtain the target product. The column chromatography eluent used was a volume ratio of 50:1 petroleum ether: ethyl acetate mixed solvent , the yield was 75%.

[0048] The structural characterization data of the product obtained in this embodiment are as follows:

[0049] 1 H NMR (400MHz, CDCl 3 )δ7.14-7.11(m, 1H), 6.51(d, J=8.5Hz, 1H), 4.96(ddd, J=5.0Hz, J=8.1Hz, J=15.9Hz, 1H), 4.33-4.21( m, 2H), 3.32(dd, J=9.1Hz, J=15.9Hz, 1H), 2.8...

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 belongs to the technical field of medicine chemical engineering synthesis, and discloses a synthetic method of fluorine-containing alkyl substituted 2,3-dihydrocoumarone derivatives and indole derivatives. The synthetic method comprises the following steps: stirring and reacting raw materials comprising a 2-allylphenol or a 2-allylaniline compound and an iodine-substituted fluorine-containing reagent in nitrogen atmosphere at 60-100 DEG C for 12-24 h with palladium as a catalyst, phosphine as a ligand, an alkali as an additive and an organic solvent as a solvent, cooling the obtained reaction solution to room temperature after the above reaction ends, carrying out extraction on the cooled reaction solution with ethyl acetate, carrying out reduced pressure solvent removal to obtain a crude product, and carrying out column chromatography purification to obtain products, wherein the equation of the reaction is represented by formula (I) shown in the description. The synthetic method for synthesizing the fluorine-containing alkyl substituted 2,3-dihydrocoumarone derivatives and indole derivatives in a one-step manner has the advantages of simplicity, easiness in implementation, mild reaction conditions, wide adaptability to a substrate, high product yield, and good industrial application prospect.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and in particular relates to a synthesis method of 2,3-dihydrobenzofuran derivatives and indole derivatives substituted by fluorine-containing alkyl groups. Background technique [0002] Difluoromethylene compounds not only have the characteristics of general fluorine-containing compounds, but also have their own unique chemical properties and medicinal value. For example, replacing hydroxyl with difluoromethylene can greatly improve the stability of the molecule in vivo and avoid adverse effects such as hydrolysis, thereby greatly improving its biological activity; at the same time, difluoromethylene can be used to simulate molecules In addition, if difluoromethylene is introduced into the statene, it can effectively inhibit the transition state analog of aspartyl protease (S.Thaisrivongs, D.T.Pals, W.M.Kati, S.R.Turner, L.M.Thomasco, J.Med . Chem. 1985, 28, 1555). ...

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): C07D307/79C07D209/26
CPCC07D209/26C07D307/79
Inventor 江焕峰廖建华伍婉卿
Owner SOUTH CHINA UNIV OF TECH
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