Preparation method of 5-trifluoromethyl-5,6-dihydrouracil

Abstract

The invention provides a preparation method of 5-trifluoromethyl-5,6-dihydrouracil. The preparation method comprises the following steps of: a) performing an addition reaction on 2-trifluoromethyl methylacrylic acid and hydrogen bromide in a solvent to obtain 3-bromo-2-trifluoromethyl methylacrylic acid; b) mixing 3-bromo-2-trifluoromethyl methylacrylic acid obtained in the step a) with ammonia water to perform an ammonolysis reaction to obtain 3-amino-2-trifluoromethyl propionic acid; and c) performing a condensation reaction on the 3-amino-2-trifluoromethyl propionic acid and a cyanate in an acidic solution to obtain 5-trifluoromethyl-5,6-dihydrouracil. The preparation method provided by the invention obtains a target product successively through hydrogen bromide addition, ammonia water ammoniation and cyanate concentration by taking 2-trifluoromethyl methylacrylic acid as an initial raw material. The preparation method is simple in technical route, mild in reaction condition, low in conventional cost of raw materials and suitable for industrial production; and moreover, the preparation method provided by the invention can greatly increase the product yield.

Description

technical field [0001] The invention relates to the technical field of fluorine chemical industry, in particular to a preparation method of 5-trifluoromethyl-5,6-dihydrouracil. Background technique [0002] 5-Trifluoromethyl-5,6-dihydrouracil is the starting material for the synthesis of many drugs, especially the important intermediates of many uracil compounds. It has been found that it has anti-tumor activity, but there is no report about it in China. The synthesis method of the compound, there are only a small number of foreign literatures reporting its synthesis method, so it is of great significance to develop an industrial route for the synthesis of 5-trifluoromethyl-5,6-dihydrouracil. [0003] At present, there are few routes for synthesizing 5-trifluoromethyl-5,6-dihydrouracil in the prior art, mainly including: [0004] (1) Patent US3201387 discloses taking 2-trifluoromethylacrylonitrile as raw material, reacting with hydrobromic acid earlier to synthesize β-bromo...

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Problems solved by technology

[0002] 5-Trifluoromethyl-5,6-dihydrouracil is the starting material for the synthesis of many drugs, especially the important intermediates of many uracil compounds. It has been found that it has anti-tumor activity, but there is no report about it in China. The synthetic method of the compound, there are only a small number of foreign literatures reporting its synthetic method, so it is of great significance to develop an industrial route for the synthesis of 5-trifluoromethyl-5,6-dihydrouracil

[0012] The above-mentioned method mainly has following disadvantages: method (1) route reaction yield is low, and industrial value is less; There are certain potential safety hazards in the use, purchase, storage and transportation at low temperature; although the yield of method (3) has increased, it needs to be reacted above 90°C, which will cause the polymerization of 2-trifluoromethacrylic acid, causing losses, and the cyclization process It will produce unknown impurities that are difficult to separate. In addition, acetic anhydride is a precursor control item, and its commercial access is narrow, which is not conducive to large-scale production and use.

[0013] Therefore, the above-mentioned method for preparing 5-trifluoromethyl-5,6-dihydrouracil has low yield and complicated process, and all have relatively large limitations, which are difficult to meet the needs of industrialized production.

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