A kind of synthetic method of 4-(difluoromethyl)-2-hydroxypyridine-5-sulfonyl chloride

A synthesis method and hydroxypyridine technology, applied in the direction of organic chemistry, etc., to achieve the effects of easy realization, high selectivity and mild reaction conditions

Active Publication Date: 2022-04-05
埃法姆(常州)生命科学技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In view of this, we propose a synthetic method for the preparation of novel fluorine-containing pyridine intermediates, which has not been reported so far

Method used

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  • A kind of synthetic method of 4-(difluoromethyl)-2-hydroxypyridine-5-sulfonyl chloride
  • A kind of synthetic method of 4-(difluoromethyl)-2-hydroxypyridine-5-sulfonyl chloride
  • A kind of synthetic method of 4-(difluoromethyl)-2-hydroxypyridine-5-sulfonyl chloride

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Experimental program
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Effect test

Embodiment 1

[0026] (1) Synthesis of Compound B

[0027] 5-Bromo-2-methoxypyridine (23g, 120mmol, 1eq.) was dissolved in 250ml of anhydrous tetrahydrofuran and set aside. Diisopropylamine (13.6g, 132mmol, 1.1eq.) was dissolved in 100ml of anhydrous tetrahydrofuran, cooled to -5°C, under nitrogen protection, n-butyl lithium (52.8ml, 132mmol, 1.1eq.) was added dropwise into the above solution. After completion of the dropwise addition, the mixture was stirred for 30 minutes.

[0028] The temperature of the above reaction system was lowered to -78°C, and a tetrahydrofuran solution of 5-bromo-2-methoxypyridine was added dropwise. After completion of the dropwise addition, the mixture was stirred for 1 hour. Then, N,N-dimethylformamide (13.4 g, 180 mmol, 1.5 eq.) was added dropwise to the above reaction system, and reacted for 2 hours.

[0029] After the reaction finished, slowly add 120ml of ammonium chloride solution in the reaction solution. It was extracted with n-hexane, and the organ...

Embodiment 2

[0044] (1) Synthesis of Compound B

[0045] 5-Bromo-2-methoxypyridine (28.8g, 150mmol, 1eq.) was dissolved in 300ml of anhydrous tetrahydrofuran and set aside. Dissolve diisopropylamine (17g, 165mmol, 1.1eq.) in 150ml of anhydrous tetrahydrofuran, cool to -5°C, and add n-butyllithium (66ml, 165mmol, 1.1eq.) dropwise to the above-mentioned in solution. After completion of the dropwise addition, the mixture was stirred for 30 minutes.

[0046] The temperature of the above reaction system was lowered to -78°C, and a tetrahydrofuran solution of 5-bromo-2-methoxypyridine was added dropwise. After completion of the dropwise addition, the mixture was stirred for 1 hour. Then, N,N-dimethylformamide (16.8 g, 225 mmol, 1.5 eq.) was added dropwise to the above reaction system, and reacted for 2 hours.

[0047] After the reaction finished, slowly add 150ml ammonium chloride solution in the reaction solution. It was extracted with n-hexane, and the organic phase was dried over anhydrous...

Embodiment 3

[0062] (1) Synthesis of Compound B

[0063] 5-Bromo-2-methoxypyridine (17.3g, 90mmol, 1eq.) was dissolved in 200ml of anhydrous tetrahydrofuran and set aside. Diisopropylamine (10.2g, 99mmol, 1.1eq.) was dissolved in 80ml of anhydrous tetrahydrofuran, cooled to -5°C, under nitrogen protection, n-butyl lithium (39.6ml, 99mmol, 1.1eq.) was added dropwise into the above solution. After completion of the dropwise addition, the mixture was stirred for 30 minutes.

[0064] The temperature of the above reaction system was lowered to -78°C, and a tetrahydrofuran solution of 5-bromo-2-methoxypyridine was added dropwise. After completion of the dropwise addition, the mixture was stirred for 1 hour. Then, N,N-dimethylformamide (10.1 g, 135 mmol, 1.5 eq.) was added dropwise to the above reaction system, and reacted for 2 hours.

[0065] After the reaction finished, slowly add 100ml of ammonium chloride solution in the reaction solution. It was extracted with n-hexane, and the organic...

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Abstract

The invention provides a method for synthesizing 4-(difluoromethyl)-2-hydroxypyridine-5-sulfonyl chloride, which belongs to the field of organic chemical synthesis. Mainly comprising the following steps: compound B is reacted with diethylaminosulfur trifluoride to obtain compound C; compound C is reacted with sodium iodide and trimethylchlorosilane to obtain compound D; under the action of alkali and catalyst, compound D React with benzyl mercaptan, 4,5-bisdiphenylphosphine-9,9-dimethylxanthene to obtain compound E; react compound E with N-chlorosuccinimide to obtain the final product compound F . The method has high selectivity, mild reaction conditions, simple synthesis operation and easy realization. In the above synthesis process, compound B is a self-made synthetic material, using 5-bromo-2-methoxypyridine as a raw material, and compound B is obtained through a nucleophilic substitution reaction.

Description

technical field [0001] The invention relates to the field of organic chemical synthesis, in particular to a synthesis method of 4-(difluoromethyl)-2-hydroxypyridine-5-sulfonyl chloride. Background technique [0002] Fluorinated pyridines are important pharmaceutical intermediates. At present, a variety of fluorine-containing compounds have been applied in the fields of pesticides and medicines. For example, fluazinam is a high-efficiency, low-toxic, broad-spectrum fungicide with insecticidal activity, which can kill mosquitoes and flies, and is safe for humans, livestock, poultry, and fish. In terms of medicine, there is talniflumate, and there is also a yellow dye intermediate, and 2,6-difluoro-3-nitropyridine has a bactericidal effect, and it has an anti-caries effect as a chewing gum additive. [0003] Using simple pyridine compounds as raw materials, introduce difluoromethyl groups that regulate lipophilicity in organisms, strong electron-donating hydroxyl groups, or s...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D213/71
CPCC07D213/71
Inventor 史建云许义波戴红升周超
Owner 埃法姆(常州)生命科学技术有限公司
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