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Synthesis method of 4,6-dichloro-5-fluoropyrimidine compound

A production method and a fluoropyrimidine technology are applied in the field of compounds with a pyrimidine structure, can solve the problems of large usage amount, many three wastes, difficult operation and the like, and achieve the effects of short reaction time, high yield and easy operation.

Active Publication Date: 2009-06-03
上海旭东海普南通药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] However, in the synthesis method reported in the above-mentioned patent, there are disadvantages such as a large amount of phosphorus oxychloride and other gases used, such as chlorine gas and phosgene with high toxicity, difficult operation, and many wastes.

Method used

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  • Synthesis method of 4,6-dichloro-5-fluoropyrimidine compound
  • Synthesis method of 4,6-dichloro-5-fluoropyrimidine compound

Examples

Experimental program
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Effect test

Embodiment 1

[0028] (1)

[0029]

[0030] Add 108 grams (2.0 mol) of sodium methylate and 1200 milliliters of methanol into a 2000 milliliter reaction flask, then add 208 grams (2.0 mol) of formamidine acetate, and heat up to reflux. 178 g (1.0 mol) of diethyl fluoroacetate was added dropwise, and the addition was completed in about 1 hour. After the addition, the reaction was kept under reflux for 8 hours. After the reflux reaction was completed, the methanol was distilled off under reduced pressure, the residue was added with 1000 ml of water, the pH was adjusted to 3-4 with concentrated hydrochloric acid, and a white solid was precipitated, dried in vacuo at 80°C to obtain 116.0 g of a white solid, the yield was 89.2%, and the purity was determined by HPLC. 96.8%.

[0031] (2)

[0032]

[0033] Add 195 grams (1.5 mol) of 4,6-dihydroxy-5-fluoropyrimidine to a 2000 ml reaction flask, 1200 ml toluene, 275 ml (3.0 mol) of phosphorus oxychloride, slowly add N, N-di 38.0 ml (0.3 mol)...

Embodiment 2

[0035] Except replacing the toluene among the embodiment 1 with trichlorethylene, all the other raw materials, formula, technique and operating procedure are all the same as the embodiment 1. 175.6 g of 4,6-dichloro-5-fluoropyrimidine was obtained. According to the amount of feed and the amount of 4,6-dichloro-5-fluoropyrimidine obtained, the calculated yield was 80.1%, and the purity was above 98%.

Embodiment 3

[0037] The molar ratio of diethyl 2-fluoropropionate, formamidine acetate and sodium methylate in step (1) is 1:1~50:1~50 (example 1:1:1, 1:25:25, 1 :50:50).

[0038] Tertiary amine catalysts are trimethylamine, triethylamine, 1,8-diazabicyclo[5.4.0]undec-7-decene, 1,4-diazabicyclo[2.2.2]octane, tetramethyl One or more of ethylenediamines, or the salts of the above-mentioned tertiary amines with hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, methanesulfonic acid, benzenesulfonic acid, maleic acid, oxalic acid or succinic acid. The molar ratio of tertiary amine catalyst to 4,6-dihydroxy-5-fluoropyrimidine is 0.01-10:1 (eg 0.01:1, 1:1, 10:1).

[0039] The solvent is benzene, dichloromethane, chloroform or carbon tetrachloride.

[0040] The chlorinating agent is thionyl chloride, sulfuryl chloride, phosphorus trichloride or phosphorus pentachloride.

[0041] All the other are the same as Example 1, the yield is greater than 80%, and the purity is ...

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Abstract

The invention discloses a method for preparing a 4,6-dichloro-5-fluoropyrimidine compound, which comprises the following steps: preparing 4,6-dihydroxy-5-fluoropyrimidine from 2-diethyl fluoropropionate and formamidine acetate in the presence of sodium methoxide; and reacting 4,6-dihydroxy-5-fluoropyrimidine with a solvent and a chlorinating agent in the presence of tertiary amine catalyst to obtain 4,6-dichloro-5-fluoropyrimidine. The invention has the advantages of simple process, low cost, environment friendly, high yield and high purity of the product.

Description

Technical areas: [0001] The present invention relates to the field of compounds with a pyrimidine structure, and in particular to a preparation method of a 4,6-dichloro-5-fluoropyrimidine compound. Background technique: [0002] In recent years, as the world's population continues to grow, the demand for crops such as wheat, rice, and corn has increased year by year. During the cultivation of the above crops, pesticides such as herbicides are increasingly widely used. [0003] 4,6-Dichloro-5-fluoropyrimidine is an important intermediate for the synthesis of the herbicide developed by Bayer Company of Germany. The sales volume of this herbicide is increasing year by year around the world. Therefore, the raw material required for its synthesis is 4,6-dichloro. The demand for -5-fluoropyrimidine is growing, with an annual demand of nearly 100 tons. It is of great significance to conduct synthetic research on it and develop new green processes suitable for industrial large-scal...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D239/30
Inventor 符爱清
Owner 上海旭东海普南通药业有限公司
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