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Preparation method of 2-fluoromethyl quinoline derivative

A technology of fluoromethylquinoline and methylquinoline, which is applied in the field of preparation of 2-fluoromethylquinoline derivatives, can solve the problems of restricting industrial application and high price, and achieve wide applicability and side reaction products Fewer, more controllable effects

Active Publication Date: 2019-07-19
UNIV OF JINAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the use of expensive AgF in the reaction process 2 , which severely limits industrial applications

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] 2-Methylquinoline (1mmol, 143mg) and Selectfluor (4mmol, 1.4g) were added to DMF solution (5ml) and reacted at 30°C for 24h, neutralized with saturated sodium bicarbonate solution, extracted with ethyl acetate (3*10mL) , combined the organic layers, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (eluent: ethyl acetate / n-hexane = 1:15) yielded 139 mg of the product 2-fluoromethylquinoline with a yield of 86%.

[0021] 1 H NMR (600 MHz, CDCl 3 ) δ 8.26 (d, J = 8.0 Hz, 1 H), 8.08 (d, J = 8.0Hz, 1H), 7.87 (d, J = 8.0 Hz, 1 H), 7.78-7.72 (m, 1 H), 7.64-7.57 (m, 2 H),5.69(d, J = 48.0 Hz, 2 H).; 13 C NMR (151 MHz, CDCl 3 ) δ 156.8 (d, J = 20.0 Hz),147.5, 137.1, 129.9, 129.1, 127.7, 127.6, 126.7, 118.2 (d, J = 5.0 Hz), 85.0(d, J = 170.0 Hz).

Embodiment 2

[0023] 2-Methyl-8-chloroquinoline (1mmol, 177mg), Selectfluor (4mmol, 1.4g) was added to DMF solution (5ml) and reacted at 30°C for 24h, neutralized with saturated sodium bicarbonate solution, extracted with ethyl acetate (3 *10 mL), the organic layers were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography (eluent: ethyl acetate / n-hexane = 1:15) yielded 131 mg of the product 2-fluoromethyl-8-chloroquinoline with a yield of 67%.

[0024] 1 H NMR (600 MHz, CDCl 3 ) δ 8.23 ​​(d, J = 8.5 Hz, 1H), 7.83 (dd, J = 7.5,1.2 Hz, 1H), 7.74 (dd, J = 8.2, 1.0 Hz, 1H), 7.67 (dd, J = 8.5, 1.1 Hz, 1H),7.45 (t, J = 7.8 Hz, 1H), 5.73 (d, J = 46.9 Hz, 2H).; 13 C NMR (151 MHz, CDCl 3 )δ 157.9 (d, J = 22.7 Hz), 143.6 (d, J = 2.2 Hz), 137.5, 133.2, 130.0 , 128.9,126.9, 126.5, 118.9 (d, J = 5.6 Hz), 84.9 (d, J = 170.5 Hz).

Embodiment 3

[0026] 2-Methyl-8-nitroquinoline (1mmol, 188mg) and Selectfluor (4mmol, 1.4g) were added to DMF solution (5ml) and reacted at 30°C for 24h, neutralized with saturated sodium bicarbonate solution, extracted with ethyl acetate (3*10mL), combined organic layers, washed with saturated brine (20mL), dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography (eluent: ethyl acetate / n-hexane = 1:15) yielded 142 mg of the product 2-fluoromethyl-8-nitroquinoline with a yield of 69%.

[0027] 1 H NMR (600 MHz, CDCl 3 ) δ 8.34 (d, J = 8.6 Hz, 1H), 8.05 (d, J = 8.2Hz, 1H), 8.02 (d, J = 7.4 Hz, 1H), 7.77 (d, J = 8.5 Hz, 1H), 7.62 (t, J = 7.9Hz, 1H), 5.67 (d, J = 46.9 Hz, 2H). 13 C NMR (151 MHz, CDCl 3 ) δ 159.9 (d, J =23.3 Hz), 148.1, 138.6 (d, J = 2.7 Hz), 137.1, 131.7, 128.4, 125.3, 123.8,119.7 (d, J = 5.9 Hz), 84.6 (d, J = 171.2 Hz).

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Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of a 2-fluoromethyl quinoline derivative. The method is implemented through the following steps: reacting 2-methylquinoline and a derivative thereof with Selectfluor in a DMF solution, and performing column chromatography to obtain a monofluoro-2-methylquinoline derivative. The method provided by the invention is carried out in the DMF solution and has good substrate solubility and wide applicability; and the reaction yield is high and the controllability is strong. The method provided by the invention is green and environment-friendly, has few side reaction products, and is green and efficient.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a preparation method of 2-fluoromethylquinoline derivatives. Background technique [0002] Organic molecules containing halogenated functional groups are an organic framework material widely used in medicinal chemistry, agricultural chemistry, and functional materials science. In addition, organohalogen compounds are also used as precursors in organic synthesis. In view of these advantages, the formation of carbon-halogen bonds has received extensive attention and tremendous progress in recent years. In particular, fluorine-containing organic molecules have become star products in many fields due to their unique steric size effect, strong bond energy, lipophilicity change, hydrogen bond acceptor, biochemical activity, and high electronegativity. [0003] Therefore, in the past decades, people have been devoted to the research of fluorination reactions, an...

Claims

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Application Information

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IPC IPC(8): C07D215/12C07D215/18
CPCC07D215/12C07D215/18
Inventor 邢姝雅刘鄢蝶于姝伟王守锋
Owner UNIV OF JINAN
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