CN102070536A - Method for preparing 2,4-dichloro-5-fluoropyrimidine compound - Google Patents
Method for preparing 2,4-dichloro-5-fluoropyrimidine compound Download PDFInfo
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- CN102070536A CN102070536A CN 201110037180 CN201110037180A CN102070536A CN 102070536 A CN102070536 A CN 102070536A CN 201110037180 CN201110037180 CN 201110037180 CN 201110037180 A CN201110037180 A CN 201110037180A CN 102070536 A CN102070536 A CN 102070536A
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Abstract
The invention discloses a method for preparing a 2,4-dichloro-5-fluoropyrimidine compound, which comprises the steps of: slowly adding 5-fluorouracil, trichloroethylene and triphosgene (bis(trichloromethyl)carbonate) into a tertiary amine catalyst at room temperature, preserving heat and performing reflux reaction for 2 to 24 hours after the adding is finished, removing a water layer and evaporating methylbenzene after the reflux is finished, and then distilling the obtained solution to obtain 2,4-dichloro-5-fluoropyrimidine. The method is an industrial method for preparing the 2,4-dichloro-5-fluoropyrimidine, and is short in reaction time and high in yield; the reaction process is performed under normal pressure, and is simple and convenient in operation; the product is high in purity, and the purity reaches over 98 percent; and the product is low in production cost, the operation is simplified in steps such as experimental operation feeding and the like, and the product has small corrosion to instruments and equipment, is equivalent to that of a product obtained by a conventional process in yield, has no wastewater containing phosphoric acid, has less three wastes, and is favorable for further promotion and application.
Description
Technical field
The present invention relates to a kind of 2, the preparation method of 4-two chloro-5-fluorine pyrimidine compounds.
Background technology
2,4-two chloro-5-fluorine pyrimidines are important intermediate of synthetic antifungal drug voriconazole etc., wherein 2, and 4-two chloro-5-fluorine pyrimidine year outputs are increasing year by year.But existing manufacturing technique is reacted complexity, troublesome poeration, product yield is low, purity is low, and there is phosphoric acid waste water to produce, pollute and how to develop simple and effective green synthesis process greatly, not only reduce production costs, can also reduce environmental pollution, accomplishing energy-saving and emission-reduction, is this area problem that need solve for a long time.
Summary of the invention
The object of the present invention is to provide a kind of simple to operate, 2 of environmental protection, the preparation method of 4-two chloro-5-fluorine pyrimidine compounds.
Technical solution of the present invention is:
A kind of 2, the preparation method of 4-two chloro-5-fluorine pyrimidine compounds is characterized in that: with 5 FU 5 fluorouracil, trieline, triphosgene (two (trichloromethyl) carbonic ether)), slowly add tertiary amine catalyst under the room temperature, finish, insulation back flow reaction 2-24 hour, backflow finishes, branch vibration layer, boil off toluene, distill then, get 2,4-two chloro-5-fluorine pyrimidines.
Described tertiary amine catalyst is Trimethylamine 99, triethylamine, N, accelerine, 1,8-diazabicyclo [5.4.0] 11-7-carbene, 1, in 4-diazabicyclo [2.2.2] octane, the Tetramethyl Ethylene Diamine one or more, or the salt of above-mentioned tertiary amine and hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetate, methanesulfonic, Phenylsulfonic acid, toxilic acid, oxalic acid or Succinic Acid formation.
Described tertiary amine catalyst is N, accelerine.
The mol ratio of described trieline, tertiary amine catalyst and 5 FU 5 fluorouracil is 1～500:0.01～10:1.
Beneficial effect of the present invention
(1) the present invention is preparation 2, the commercial run of 4-dichloro 5-fluorine pyrimidine;
(2) reaction times weak point, the yield height;
(3) reaction process is carried out under normal pressure, and is easy and simple to handle;
(5) product purity height, purity reaches more than 98%;
(6) production cost of products is cheap, simplifies the operation in steps such as experimental implementation is reinforced, and is little to plant and instrument corrodibility, and yield is suitable with old technology, and do not have the waste water generation of phosphoric acid, and the three wastes are less, help further applying.
The invention will be further described below in conjunction with embodiment.
Embodiment
Embodiment 1:
A kind of 2, the preparation method of 4-two chloro-5-fluorine pyrimidine compounds is with 5 FU 5 fluorouracil, trieline, two (trichloromethyl) carbonic ether) (being triphosgene), slowly add tertiary amine catalyst N under the room temperature, accelerine finishes, insulation back flow reaction 2-24 hour, backflow finishes, branch vibration layer boils off toluene, distills then, get 2,4-two chloro-5-fluorine pyrimidines.
The mol ratio of described trieline, tertiary amine catalyst and 5 FU 5 fluorouracil is 1～500:0.01～10:1(example 1:5:1,200:0.1:1,500:10:1).
Product purity reaches more than 99%.
Embodiment 2:
Tertiary amine catalyst is Trimethylamine 99, triethylamine, 1,8-diazabicyclo [5.4.0] 11-7-carbene, 1, in 4-diazabicyclo [2.2.2] octane, the Tetramethyl Ethylene Diamine one or more, or the salt of above-mentioned tertiary amine and hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetate, methanesulfonic, Phenylsulfonic acid, toxilic acid, oxalic acid or Succinic Acid formation.All the other are with embodiment 1.
Product purity reaches more than 98%.
Claims (4)
1. one kind 2, the preparation method of 4-two chloro-5-fluorine pyrimidine compounds is characterized in that: with 5 FU 5 fluorouracil, trieline, triphosgene, slowly add tertiary amine catalyst under the room temperature, finish, insulation back flow reaction 2-24 hour, backflow finishes, branch vibration layer, boil off toluene, distill then, get 2,4-two chloro-5-fluorine pyrimidines.
2. according to claim 12, the preparation method of 4-two chloro-5-fluorine pyrimidine compounds, it is characterized in that: described tertiary amine catalyst is Trimethylamine 99, triethylamine, N, accelerine, 1,8-diazabicyclo [5.4.0] 11-7-carbene, 1, in 4-diazabicyclo [2.2.2] octane, the Tetramethyl Ethylene Diamine one or more, or the salt of above-mentioned tertiary amine and hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetate, methanesulfonic, Phenylsulfonic acid, toxilic acid, oxalic acid or Succinic Acid formation.
3. according to claim 22, the preparation method of 4-two chloro-5-fluorine pyrimidine compounds, it is characterized in that: described tertiary amine catalyst is N, accelerine.
4. according to claim 1,2 or 3 described 2, the preparation method of 4-two chloro-5-fluorine pyrimidine compounds, it is characterized in that: the mol ratio of described trieline, tertiary amine catalyst and 5 FU 5 fluorouracil is 1～500:0.01～10:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110037180 CN102070536A (en) | 2011-02-14 | 2011-02-14 | Method for preparing 2,4-dichloro-5-fluoropyrimidine compound |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 201110037180 CN102070536A (en) | 2011-02-14 | 2011-02-14 | Method for preparing 2,4-dichloro-5-fluoropyrimidine compound |
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| CN102070536A true CN102070536A (en) | 2011-05-25 |
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| CN 201110037180 Pending CN102070536A (en) | 2011-02-14 | 2011-02-14 | Method for preparing 2,4-dichloro-5-fluoropyrimidine compound |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646368A (en) * | 2016-03-03 | 2016-06-08 | 深圳诺普信农化股份有限公司 | Preparation method of 2, 4-dichloro-5-methoxy pyrimidine |
| CN109776426A (en) * | 2019-03-18 | 2019-05-21 | 河南中医药大学 | A method of the preparation chloro- 5-FU of 2,4- bis- is reacted using ultraviolet catalytic |
| CN110204495A (en) * | 2019-06-03 | 2019-09-06 | 浙江工业大学 | A kind of preparation method of chloro polyhydroxy nitrogen heteroaromatic rings compound |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1687036A (en) * | 2005-06-20 | 2005-10-26 | 江苏省激素研究所有限公司 | Method for preparing 4,6 dichloropyridine |
| CN101445485A (en) * | 2008-12-31 | 2009-06-03 | 符爱清 | Synthesis method of 4,6-dichloro-5-fluoropyrimidine compound |
-
2011
- 2011-02-14 CN CN 201110037180 patent/CN102070536A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1687036A (en) * | 2005-06-20 | 2005-10-26 | 江苏省激素研究所有限公司 | Method for preparing 4,6 dichloropyridine |
| CN101445485A (en) * | 2008-12-31 | 2009-06-03 | 符爱清 | Synthesis method of 4,6-dichloro-5-fluoropyrimidine compound |
Non-Patent Citations (1)
| Title |
|---|
| 《贵阳医学院学报》 20060831 谢珺等 2-苄氧基-5-氟-4-嘧啶酮-3-丁酸乙酯的合成及结构鉴定 第340页 1-4 第31卷, 第4期 2 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646368A (en) * | 2016-03-03 | 2016-06-08 | 深圳诺普信农化股份有限公司 | Preparation method of 2, 4-dichloro-5-methoxy pyrimidine |
| CN109776426A (en) * | 2019-03-18 | 2019-05-21 | 河南中医药大学 | A method of the preparation chloro- 5-FU of 2,4- bis- is reacted using ultraviolet catalytic |
| CN109776426B (en) * | 2019-03-18 | 2022-03-01 | 河南中医药大学 | Method for preparing 2, 4-dichloro-5-fluoropyrimidine by utilizing ultraviolet light catalytic reaction |
| CN110204495A (en) * | 2019-06-03 | 2019-09-06 | 浙江工业大学 | A kind of preparation method of chloro polyhydroxy nitrogen heteroaromatic rings compound |
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Application publication date: 20110525 |