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Preparation method of 4-(2',2'2'-trifluoro)ethylquinoline series

A technology of ethylquinoline and trifluoromethyl, applied in the field of preparation of 4-ethylquinoline derivatives, can solve the problems of low yield of target product, harsh conditions, poor reaction selectivity, etc., and achieve chemoselectivity Excellent, simple reaction operation, and good product yield

Active Publication Date: 2017-01-25
JIANGXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As we all know, the Friedel-Crafts alkylation reaction has disadvantages such as harsh conditions, poor selectivity of the reaction, and low yield of the target product.

Method used

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  • Preparation method of 4-(2',2'2'-trifluoro)ethylquinoline series
  • Preparation method of 4-(2',2'2'-trifluoro)ethylquinoline series
  • Preparation method of 4-(2',2'2'-trifluoro)ethylquinoline series

Examples

Experimental program
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Effect test

example 1

[0019]

[0020] In a 25mL Schlenk reaction tube equipped with a magnetic stir bar, add N-(2-ethynylphenyl)enamine-2,3-dicarboxylic acid methyl ester (0.2mmol, 1.0eq.), 1-(trifluoro Methyl)-1,2-phenyliodide-3(1H)-one (Togni's reagent) (0.4mmol, 2.0eq.), cuprous oxide (0.04mmol, 20mol%), pyridine (0.6mmol, 3.0eq. ) and 1,2-dichloroethane (2 mL), the reaction tube was placed in a heating module at 70° C., heated and stirred for 24-36 h, and TLC detected that the reaction was complete. After the reaction solution was cooled to room temperature, it was washed with saturated sodium bicarbonate solution, extracted three times with ethyl acetate, the organic layers were combined, dried with anhydrous sodium sulfate, filtered, added a small amount of silica gel, spin-dried, and the crude product was subjected to flash column chromatography Separation and purification gave methyl 4-(2',2',2'-trifluoro)ethylquinoline-2,3-dicarboxylate 3a with a yield of 61%.

[0021] 1 H NMR (400MHz...

example 2

[0024]

[0025]In a 25mL Schlenk reaction tube equipped with a magnetic stirrer, add methyl N-(2-ethynyl-4-fluoro-phenyl)enamine-2,3-dicarboxylate (0.2mmol, 1.0eq.), Togni's reagent (0.4mmol, 2.0eq.), cuprous oxide (0.04mmol, 20mol%), pyridine (0.6mmol, 3.0eq.) and 1,2-dichloroethane (2mL) put the reaction tube at 70°C In the heating module, react for 24-36h, and TLC detects that the reaction is complete. After the reaction solution was cooled to room temperature, it was washed with saturated sodium bicarbonate solution, extracted three times with ethyl acetate, the organic layers were combined, dried with anhydrous sodium sulfate, filtered, added a small amount of silica gel, spin-dried, and the crude product was subjected to flash column chromatography Separation and purification gave methyl 6-fluoro-4-(2',2',2'-trifluoro)ethylquinoline-2,3-dicarboxylate 3b with a yield of 45%.

[0026] 1 H NMR (400MHz, CDCl 3 )δ3.96(s,3H),4.04(s,3H),4.13(q,J=10.0Hz,2H),7.67-7.59(m,1H)...

example 3

[0029]

[0030] In a 25mL Schlenk reaction tube equipped with a magnetic stirrer, add methyl N-(2-ethynyl-4-isopropyl-phenyl)enamine-2,3-dicarboxylate (0.2mmol, 1.0eq. ), Togni's reagent (0.4mmol, 2.0eq.), cuprous oxide (0.04mmol, 20mol%), pyridine (0.6mmol, 3.0eq.) and 1,2-dichloroethane (2mL) put the reaction tube in In a heating module at 70°C, react for 24-36h, and the reaction is complete as detected by TLC. After the reaction solution was cooled to room temperature, it was washed with saturated sodium bicarbonate solution, extracted three times with ethyl acetate, the organic layers were combined, dried with anhydrous sodium sulfate, filtered, added a small amount of silica gel, spin-dried, and the crude product was subjected to flash column chromatography Separation and purification gave methyl 6-isopropyl-4-(2',2',2'-trifluoro)ethylquinoline-2,3-dicarboxylate 3c with a yield of 56%.

[0031] 1 H NMR (400MHz, CDCl 3 )δ1.45-1.30(m,6H),3.15(s,3H),3.95(s,3H),4.04(s,3...

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Abstract

The invention discloses a preparation method of 4-(2',2'2'-trifluoro)ethylquinoline series. The preparation method includes adopting N-(2-ethynyl aryl)enamine as a reaction substrate, and enabling the N-(2-ethynyl aryl)enamine and a trifluoromethylation reagent to undergo trifluoromethylation and cyclization reaction for 24-36 hours in an organic solvent under catalysis of transition metal copper under an alkaline condition so as to obtain the 4-(2',2'2'-trifluoro)ethylquinoline series by a cascade cyclization reaction policy. The preparation method has the advantages that the preparation method is high in selectivity, simple and convenient to operate, high in product purity and convenient to separate and purify, and the 4-(2',2'2'-trifluoro)ethylquinoline series are novel in structure (confirmed by characterizations such as 1H, NMR, 13C NMR, 19F NMR and HRMS), have potential biological activity and pharmaceutical activity and can be further synthesized into compounds more complex in structure and widely used in the fields of pesticides and pharmaceuticals as intermediates.

Description

technical field [0001] The invention belongs to the technical field of organic chemistry, and in particular relates to a preparation method of 4-(2',2',2'-trifluoro)ethylquinoline derivatives. Background technique [0002] Trifluoromethylquinoline compound is an important fluorine-containing heterocyclic compound, and has good biological activity and pharmacological activity ((a) Müller, K.; Faeh, C.; Diederich, F.Science 2007,317 ,1881-1886; (b) Wang, J.; Sánchez-Roselló, M.; J.L.; Delpozo, C.; Sorochinsky, A.E.; Fustero, S.; Soloshonok, V.A.; Liu, H. Chem. Rev. 2014, 114, 2432-2506.). Fluorine-containing heterocyclic compounds have been widely used in the field of medicine. For example, Casodex, Efavirena, and Halothane are all clinical therapeutic drugs ((a) Baker, A.Inventory of Industrial Fluro-Biochemicals, Eyrolles, Paris.1997; (b) Lal, G.S.Chem.Commun.1999, 215-216; ( c) James, K.D.; Ekwunbe, N.N. Synthesis 2002, 850-852.). In addition, in the field of pesticide...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D215/54
CPCC07D215/54
Inventor 丁秋平陈文帆彭以元
Owner JIANGXI NORMAL UNIV
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