Preparation method of 6-chloro-7-ethyl-4-hydroxyquinoline

Abstract

The invention discloses a preparation method of 6-chloro-7-ethyl-4-hydroxyquinoline. A target product is obtained by carrying out nitration, reduction and cyclization on 1-(3-chloro-4-ethylphenyl)ethyl ketone serving as a starting raw material. The compound is an important medical intermediate.

Description

technical field

[0001] The invention relates to a novel preparation method of a pharmaceutical intermediate, in particular to a preparation method of 6-chloro-7-ethyl-4-hydroxyquinoline. technical background

[0002] Compound 6-chloro-7-ethyl-4-hydroxyquinoline, the structural formula is:

[0003]

[0004] The compound 6-chloro-7-ethyl-4-hydroxyquinoline and related derivatives are widely used in medicinal chemistry and organic synthesis. The synthesis of 6-chloro-7-ethyl-4-hydroxyquinoline is relatively difficult at present. Therefore, it is necessary to develop a synthetic method with easy-to-obtain raw materials, convenient operation, easy-to-control reaction and suitable overall yield. Contents of the invention

[0005] The invention discloses a method for preparing 6-chloro-7-ethyl-4-hydroxyquinoline, which uses 1-(3-chloro-4-ethylphenyl)ethanone as a starting material, and undergoes nitration and reduction , ring closure to obtain the target product 4, the synt...

Examples

Embodiment 1

[0019] (1) Synthesis of 1-(5-chloro-4-ethyl-2-nitrophenyl)ethanone

[0020] Add 29g of 1-(3-chloro-4-ethylphenyl)ethanone to 260ml of acetic acid, add 62g of concentrated nitric acid, stir overnight at room temperature, concentrate, then add ethyl acetate and water, separate, dry, concentrate, and the remaining The material was separated on a column to obtain 31 g of 1-(5-chloro-4-ethyl-2-nitrophenyl)ethanone.

[0021] (2) Synthesis of 1-(2-amino-5-chloro-4-ethylphenyl)ethanone

[0022] Add 30g of 1-(4,5-diethyl-2-nitrophenyl)ethanone to 240ml of anhydrous methanol, then add 4g of 10% palladium carbon, pass in hydrogen, stir at room temperature for 4 hours, filter, and collect the filtrate , concentrated to give 22g of 1-(2-amino-5-chloro-4-ethylphenyl)ethanone.

[0023] (3) Synthesis of 6-chloro-7-ethyl-4-hydroxyquinoline

[0024] Add 12g of sodium to 230ml of absolute ethanol, then add 20g of 1-(2-amino-5-chloro-4-ethylphenyl)ethanone and 32g of ethyl formate, heat under ...

technical field

[0001] The invention relates to a novel preparation method of a pharmaceutical intermediate, in particular to a preparation method of 6-chloro-7-ethyl-4-hydroxyquinoline. technical background

[0002] Compound 6-chloro-7-ethyl-4-hydroxyquinoline, the structural formula is:

[0003]

[0004] The compound 6-chloro-7-ethyl-4-hydroxyquinoline and related derivatives are widely used in medicinal chemistry and organic synthesis. The synthesis of 6-chloro-7-ethyl-4-hydroxyquinoline is relatively difficult at present. Therefore, it is necessary to develop a synthetic method with easy-to-obtain raw materials, convenient operation, easy-to-control reaction and suitable overall yield. Contents of the invention

[0005] The invention discloses a method for preparing 6-chloro-7-ethyl-4-hydroxyquinoline, which uses 1-(3-chloro-4-ethylphenyl)ethanone as a starting material, and undergoes nitration and reduction , ring closure to obtain the target product 4, the synt...

Examples

Embodiment 1

[0019] (1) Synthesis of 1-(5-chloro-4-ethyl-2-nitrophenyl)ethanone

[0020] Add 29g of 1-(3-chloro-4-ethylphenyl)ethanone to 260ml of acetic acid, add 62g of concentrated nitric acid, stir overnight at room temperature, concentrate, then add ethyl acetate and water, separate, dry, concentrate, and the remaining The material was separated on a column to obtain 31 g of 1-(5-chloro-4-ethyl-2-nitrophenyl)ethanone.

[0021] (2) Synthesis of 1-(2-amino-5-chloro-4-ethylphenyl)ethanone

[0022] Add 30g of 1-(4,5-diethyl-2-nitrophenyl)ethanone to 240ml of anhydrous methanol, then add 4g of 10% palladium carbon, pass in hydrogen, stir at room temperature for 4 hours, filter, and collect the filtrate , concentrated to give 22g of 1-(2-amino-5-chloro-4-ethylphenyl)ethanone.

[0023] (3) Synthesis of 6-chloro-7-ethyl-4-hydroxyquinoline

[0024] Add 12g of sodium to 230ml of absolute ethanol, then add 20g of 1-(2-amino-5-chloro-4-ethylphenyl)ethanone and 32g of ethyl formate, heat under ...

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