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Preparation method of 4, 6-dichloro-5-fluoropyrimidine

A technology of fluoropyrimidine and chlorine flow, which is applied in 4 fields, can solve the problems of complex production process reaction, phosphoric acid-containing wastewater, and low product yield, and achieve significant economic and social benefits, no waste residue, and high product purity.

Pending Publication Date: 2022-08-09
江苏中渊化学品有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing production process has complex reactions, troublesome operation, low product yield, low purity, and waste water containing phosphoric acid, which causes great pollution. How to develop a simple and effective green synthesis process can not only reduce production costs, but also reduce environmental pollution. From energy saving to emission reduction, it has been a problem that needs to be solved in this field for a long time

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] A method for preparing 4,6-dichloro-5-fluoropyrimidine, using isopentafluorine as a starting material, immersing in a dichloromethane solvent, slowly adding catalyst sulfonyl chloride, and the addition amount is 4,6-dichloropyrimidine 2% of the mass of 5-fluoropyrimidine was irradiated with ultraviolet light with a wavelength of 220 nm for 12 minutes, and then chlorine gas was introduced, the reaction temperature was 20-25 ° C, the chlorine was stirred for 9 hours, the reaction was kept under reflux for 6 hours, the reflux was completed, and the water was separated. layer, evaporated the toluene, and then distilled to obtain 4,6-dichloro-5-fluoropyrimidine mother liquor. After washing the 4,6-dichloro-5-fluoropyrimidine mother liquor with aqueous hydrochloric acid to remove impurities, the product was precipitated again; the product purity was 99.3 %, the total yield is 96%.

Embodiment 2

[0017] A preparation method of 4,6-dichloro-5-fluoropyrimidine, using isopentafluorine as starting material, immersing in dichloroethane solvent, slowly adding catalyst sulfonyl chloride, and the addition amount is 4,6-dichloroethane 4% of the mass of chloro-5-fluoropyrimidine was irradiated with ultraviolet light with a wavelength of 280 nm for 20 minutes, and chlorine gas was introduced, the reaction temperature was 25 ° C, and the chlorine was stirred for 10 hours, and the reaction was kept under reflux for 22 hours. , evaporated the toluene, and then distilled to get the 4,6-dichloro-5-fluoropyrimidine mother liquor. After washing the 4,6-dichloro-5-fluoropyrimidine mother liquor with aqueous sulfuric acid to remove impurities, the product was precipitated again; the product purity was 99.5% , the total yield is 97%.

Embodiment 3

[0019] A method for preparing 4,6-dichloro-5-fluoropyrimidine, using isopentafluorine as a starting material, immersing it in a chloroform solvent, slowly adding catalyst sulfonyl chloride, and the addition amount is 4,6-dichloro-5 -3% of the mass of fluoropyrimidine, irradiated with ultraviolet light with a wavelength of 260 nm for 17 minutes, passed chlorine gas, the reaction temperature was 23 ° C, passed chlorine and stirred for 9 hours, and kept the reflux reaction for 15 hours. Toluene was removed, and then distilled to obtain 4,6-dichloro-5-fluoropyrimidine mother liquor. The 4,6-dichloro-5-fluoropyrimidine mother liquor was washed with citric acid aqueous solution to remove impurities, and the product was precipitated again; the product purity was 99.8% , the total yield is 97%.

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Abstract

The invention discloses a preparation method of 4, 6-dichloro-5-fluoropyrimidine, which comprises the following steps: by taking isopentafluoride as a starting raw material, immersing the starting raw material into a solvent, slowly adding a catalyst, irradiating with ultraviolet light for 12-20 minutes, introducing chlorine, reacting at 20-25 DEG C, introducing chlorine, stirring for 9-10 hours, keeping the temperature, carrying out reflux reaction for 2-24 hours, separating a water layer after the reflux is finished, evaporating to remove methylbenzene, and distilling to obtain the 4, 6-dichloro-5-fluoropyrimidine. The invention discloses a 2, 6-dichloro-5-fluoropyrimidine mother liquor. The method has the advantages of simple and easy process, mild conditions, low cost, no waste residue, effective prevention of environmental pollution, substantial economic and social benefits, high purity of the obtained product, and suitableness for industrial production.

Description

technical field [0001] The invention relates to the technical field of medicine and chemical industry, in particular to a preparation method of 4,6-dichloro-5-fluoropyrimidine. Background technique [0002] 4,6-Dichloro-5-fluoropyrimidine is an important intermediate in the synthesis of antifungal drugs such as voriconazole, among which the annual production of 4,6-dichloro-5-fluoropyrimidine is increasing year by year. However, the existing production process has complex reaction, troublesome operation, low product yield and low purity, and generates phosphoric acid-containing waste water. How to develop a simple and effective green synthesis process can not only reduce production costs, but also reduce environmental pollution. Energy saving and emission reduction is a problem that needs to be solved in this field for a long time. SUMMARY OF THE INVENTION [0003] The object of the present invention is to provide a preparation method of 4,6-dichloro-5-fluoropyrimidine in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D239/30
CPCC07D239/30Y02P20/584
Inventor 朱敏亮肖元超顾健瑸陈建国
Owner 江苏中渊化学品有限公司