A kind of method of electron-rich five-membered heterocyclic acid and its derivative decarboxylation and fluorine

A five-membered heterocyclic, electron-rich technology, applied in organic chemistry and other fields, can solve problems in the field of organic reactions, such as to be completed, and achieve the effects of optimization of reaction conditions and parameters, high product yield, and simple steps

Inactive Publication Date: 2019-04-05
CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In patent document 201610065056.4, a method for decarboxylation and fluorine addition to cinnamic acid and its derivatives has been disclosed, but the fluorination and decarboxylation of carboxylic acids directly connected to SP2 hybridized carbon atoms on electron-rich heterocycles has never been reported. The field of organic reactions needs to be completed

Method used

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  • A kind of method of electron-rich five-membered heterocyclic acid and its derivative decarboxylation and fluorine
  • A kind of method of electron-rich five-membered heterocyclic acid and its derivative decarboxylation and fluorine
  • A kind of method of electron-rich five-membered heterocyclic acid and its derivative decarboxylation and fluorine

Examples

Experimental program
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Effect test

Embodiment 1

[0055] Synthesis, separation and purification of 2-fluorobenzofuran: Add benzofuran-2-carboxylic acid (162mg, 1.0mmol, 1.0eq) and (708mg, 2.0mmol, 2.0eq), potassium fluoride (232mg, 4.0mmol, 4.0eq); then add dichloroethane (3.3mL) and water (1.7mL) as a solvent; place the reaction bottle at 70°C Heat and stir the reaction in an oil bath pot for 15 hours; after the reaction is completed, extract the reaction mixture system twice with 20 mL ether, combine the organic phases and wash with saturated brine, and then add anhydrous sodium sulfate to dry; after drying, spin dry under reduced pressure organic solvent to obtain a crude product; the crude product was subjected to column separation using analytically pure n-pentane as the eluent to obtain the final product: 2-fluorobenzofuran was a yellow oily liquid with a yield of 75%.

[0056] 1 H NMR (400MHz, CDCl 3 ):δ7.50-7.48(m,1H),7.42-7.40(m,1H),7.28-7.25(m,2H),5.87(dd,J=0.7Hz,6.5Hz,1H). 13 C NMR (100MHz, CDCl 3 ): δ160.6(d,...

Embodiment 2

[0060] Synthesis, separation and purification of 2-fluoro-3-methylbenzofuran: 3-methylbenzofuran-2-carboxylic acid (176mg, 1.0mmol, 1.0 eq), (708mg, 2.0mmol, 2.0eq), potassium fluoride (232mg, 4.0mmol, 4.0eq); then add dichloroethane (3.3mL) and water (1.7mL) as a solvent; place the reaction bottle at 70°C Heat and stir the reaction in an oil bath pot for 15 hours; after the reaction is completed, extract the reaction mixture system twice with 20 mL ether, combine the organic phases and wash with saturated brine, and then add anhydrous sodium sulfate to dry; after drying, spin dry under reduced pressure organic solvent to obtain the crude product; the crude product was separated by column using analytically pure n-pentane as the eluent to obtain the final product: 2-fluoro-3-methylbenzofuran was a light yellow oily liquid with a yield of 63 %.

[0061] 1 H NMR (400MHz, CDCl 3 ): δ7.42-7.40(m,1H),7.36-7.34(m,1H),7.26-7.23(m,2H),2.12(d,J=1.6Hz,3H). 13 C NMR (100MHz, CDCl ...

Embodiment 3

[0065] Synthesis, separation and purification of 5-bromo-2-fluorobenzofuran: 5-bromobenzofuran-2-carboxylic acid (240mg, 1.0mmol, 1.0eq) was successively added into a 50mL round bottom flask equipped with a magnetic stirrer , (708mg, 2.0mmol, 2.0eq), potassium fluoride (232mg, 4.0mmol, 4.0eq); then add dichloroethane (3.3mL) and water (1.7mL) as a solvent; place the reaction bottle at 70°C Heat and stir the reaction in an oil bath pot for 15 hours; after the reaction is completed, extract the reaction mixture system twice with 20 mL ether, combine the organic phases and wash with saturated brine, and then add anhydrous sodium sulfate to dry; after drying, spin dry under reduced pressure Organic solvent to obtain the crude product; the crude product was separated by column using analytically pure n-pentane as the eluent to obtain the final product: 5-bromo-2-fluorobenzofuran was light yellow oily liquid with a yield of 62% .

[0066] 1 H NMR (400MHz, CDCl 3 ): δ7.59(d, J=2...

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PUM

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Abstract

The invention provides electron-rich five-membered heterocyclic acid and a method for decarboxylation and fluorination of derivatives thereof. High-efficiency decarboxylation and fluorination are performed on the electron-rich five-membered heterocyclic acid with different kinds of electron-rich five-membered heterocycles connected with carboxylic acid directly, and the derivatives of the electron-rich five-membered heterocyclic acid, An obtained product has high yield and the process is simple.

Description

technical field [0001] The invention relates to a method for decarboxylation and fluorination of electron-rich five-membered heterocyclic acids and derivatives thereof, and belongs to the field of synthesis of fluorine-containing drug intermediates. Background technique [0002] Carboxylic acid compounds widely exist in nature, and many natural organic compounds contain carboxyl functional groups. Due to its low cost and easy decarboxylation, carboxylic acid compounds are widely used as substrates in the field of organic synthesis, and the significance of free radical fluorination decarboxylation reaction has become more and more important. [0003] Fluorine atoms play an irreplaceable role in the field of organic polymer modification. At the same time, fluorine-containing drugs account for a considerable share of known marketed drugs, which is mainly due to the special properties of fluorine atoms. As the most electronegative atom in the periodic table of elements, when a ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D307/82C07D333/28C07D333/62C07D231/56C07D231/16C07D209/30
CPCC07D209/30C07D231/16C07D231/56C07D307/82C07D333/28C07D333/62
Inventor 唐真宇袁希姚剑飞
Owner CENT SOUTH UNIV
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