A kind of synthetic method of 2-fluoro-5-trifluoromethylpyrimidine

A technology of trifluoromethylpyrimidine and a synthesis method, applied in the field of drug synthesis, can solve the problems of high cost of raw materials, complicated process and high cost of antimony pentafluoride

Active Publication Date: 2022-08-05
KINGCHEM LIAONING CHEMICAL CO LTD
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0009] The disadvantage of this method is that carbon tetrachloride, which is prohibited by the "Montreal Protocol", is used as a solvent, and sulfone chloride is used for chlorination. The cost of sulfone chloride is much higher than that of chlorine, and the cost of antimony pentafluoride is also very high. and heavy metal pollution
[0010] In a word, the methods for synthesizing 2-fluoro-5-trifluoromethylpyrimidine in the present art have problems such as complex process, high cost of raw materials, low yield, etc.

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  • A kind of synthetic method of 2-fluoro-5-trifluoromethylpyrimidine
  • A kind of synthetic method of 2-fluoro-5-trifluoromethylpyrimidine
  • A kind of synthetic method of 2-fluoro-5-trifluoromethylpyrimidine

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[0029] The invention provides a method for synthesizing 2-fluoro-5-trifluoromethylpyrimidine, comprising the following steps:

[0030] Mixing 5-methyluracil, phosphorus oxychloride and phosphorus pentachloride for cyclic chlorination to obtain 2,4-dichloro-5-methylpyrimidine;

[0031] Mixing the 2,4-dichloro-5-methylpyrimidine and zinc powder to carry out a reduction reaction to obtain 2-chloro-5-methylpyrimidine;

[0032] Mixing the 2-chloro-5-methylpyrimidine with an initiator, and introducing chlorine gas to carry out a chlorination reaction to obtain 2-chloro-5-trichloromethylpyrimidine;

[0033] The 2-chloro-5-trichloromethylpyrimidine and hydrogen fluoride are mixed for a fluorination reaction to obtain 2-fluoro-5-trifluoromethylpyrimidine.

[0034] In the present invention, 5-methyluracil, phosphorus oxychloride and phosphorus pentachloride are mixed for cyclic chlorination reaction to obtain 2,4-dichloro-5-methylpyrimidine. In the present invention, the molar ratio o...

Embodiment 1

[0057] Take 75 g (0.59 mol) of 5-methyluracil, 236 g of phosphorus oxychloride, and 16.5 g (0.12 mol) of triethylamine hydrochloride, add them to the reaction flask, heat up to 100 ℃ ~ 110 ℃, reflux for 5 hours, The temperature was lowered to 40°C, phosphorus pentachloride 248 (1.19 mol) was added, and the reaction was maintained for 2 h. After the reaction was completed, phosphorus oxychloride was recovered by distillation under reduced pressure, and the distillation was continued under reduced pressure to obtain 88 g (0.54 mol) of 2,4-dichloro-5-methylpyrimidine with a yield of 91.5%.

Embodiment 2

[0059] Take 70 g (0.43 mol) of 2,4-dichloro-5-methylpyrimidine obtained in Example 1, 84 g (1.28 mol) of zinc powder, and 700 g of water, add them to a reaction flask, and conduct a reflux reaction at 95°C to 105°C for 5 hours. After the reaction is completed, the product feed liquid is extracted with dichloromethane, the dichloromethane phase is distilled to recover dichloromethane, and the obtained crude product is recrystallized with petroleum ether to obtain 45 g (0.35 mol) of 2-chloro-5-methylpyrimidine. ), the yield was 81.4%.

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Abstract

The invention relates to the technical field of drug synthesis, and provides a method for synthesizing 2-fluoro-5-trifluoromethylpyrimidine. The invention uses 5-methyluracil as a raw material, and obtains the target product through a cyclic chlorination reaction, a reduction reaction, a chlorination reaction and a fluorination reaction, the process is simple, the raw materials are cheap and easy to obtain, the yield is high, and no generation of Heavy metal pollution; and the present invention uses phosphorus oxychloride to perform chlorination in the cyclic chlorination reaction, and uses chlorine to perform chlorination in the chlorination reaction, and the costs of both are relatively low, and phosphorus pentachloride is used in the cyclic chlorination reaction. Recovering phosphorus oxychloride can further reduce the reaction cost.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a method for synthesizing 2-fluoro-5-trifluoromethylpyrimidine. Background technique [0002] 2-Fluoro-5-trifluoromethylpyrimidine is an important intermediate in the synthesis of pharmaceuticals, which can be used to synthesize fused-ring dihydrofuran compounds, which can be used as G protein-coupled receptor GPR119 modulators, For the treatment of diabetes, obesity and dyslipidemia diseases. In addition, 2-fluoro-5-trifluoromethylpyrimidine can also be used as an intermediate in the synthesis of drugs for Alzheimer's disease and schizophrenia. [0003] At present, the synthetic method of 2-fluoro-5-trifluoromethylpyrimidine reported in this area mainly includes the following several: [0004] Patent WO2009150240A introduces a method for synthesizing -fluoro-5-trifluoromethylpyrimidine, wherein 2,4-dichloro-5-trifluoromethylpyrimidine is used as a raw material, and zinc...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D239/30
CPCC07D239/30
Inventor 付立民何秉恕胡珍珠宋桐集王新宇
Owner KINGCHEM LIAONING CHEMICAL CO LTD
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