Method for fluorinating pyrimidine derivative by using micro-channel reactor

A technology of microchannel reactor and pyrimidine derivatives, which is applied in the field of fluorination of pyrimidine derivatives, can solve the problems of difficult production process, long route, low yield, etc., achieve high conversion rate and selectivity, simplify the purification process, and produce The effect of high purity

Inactive Publication Date: 2017-02-22
ZHEJIANG RES INST OF CHEM IND CO LTD +1
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  • Abstract
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  • Application Information

AI Technical Summary

Problems solved by technology

Condensation cyclization method first condenses enol sodium salt of fluoroformoacetate with urea or its derivatives to form a ring, and then performs post-treatment to obtain the corresponding product. This method has a long route, low yield, and great difficulty in product purification.
The direct

Method used

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  • Method for fluorinating pyrimidine derivative by using micro-channel reactor
  • Method for fluorinating pyrimidine derivative by using micro-channel reactor
  • Method for fluorinating pyrimidine derivative by using micro-channel reactor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] optional attachment figure 2 1 medium corning straight channel module (as a pre-mixing preheating module), 6 corning "heart-shaped" microchannel reaction modules, 1 corning straight channel module (as a quenching module) and 8 heat transfer modules, according to the attached image 3 The reaction process shown constitutes a continuous flow microchannel reaction system. Heat transfer oil is used as the reaction heat exchange medium. According to the forced heat transfer principle of the microchannel reactor, only two temperature measuring points are set at the reactor inlet and outlet. Before the reaction, the microchannel reaction system and connecting pipelines were dewatered and degreased respectively, and the system and connecting pipelines were passivated with fluorine gas with 5mol% fluorine-nitrogen mixed gas, and the air tightness inspection was carried out at 1.0MPa. by attaching image 3 A liquid-phase pump (such as a diaphragm metering pump) in the microchan...

Embodiment 2

[0033] Use the same Corning microchannel reactor as in Example 1, and follow the same connection and control methods. In this example, the reaction conditions were changed.

[0034] Set the temperature of the heat exchanger to -5°C, which is the reaction temperature. Set the reaction pressure to 0.1MPa. The reaction raw material 2 is a uracil solution, that is, a mixture of uracil and trifluoroacetic acid, the mass concentration of uracil is 7%, and the feed rate is 100 g / min. Raw material 1 is 30mol% fluorine-nitrogen mixed gas, and the feed rate is 4.67L / min. The molar ratio of fluorine gas to uracil is 1:1.

[0035]The reaction raw material 2 uracil solution enters the "heart-shaped" micro-channel reaction module 4 after passing through the micro-channel premixing and preheating module 3, and the fluorine-nitrogen mixed gas directly enters the micro-channel reaction module 4 through the gas mass flow meter, and enters the "heart-shaped" micro-channel reaction module 4 di...

Embodiment 3

[0038] Use the same Corning microchannel reactor as in Example 1, and follow the same connection and control methods. In this example, the reaction conditions were changed.

[0039] Set the heat exchanger temperature to 50°C, which is the reaction temperature. Set the reaction pressure to 0.3MPa. The reaction raw material 2 is a uracil solution, i.e. a mixture of uracil, trifluoroacetic acid and anhydrous hydrofluoric acid, with a mass concentration of uracil of 15%, wherein the mass ratio of trifluoroacetic acid to anhydrous hydrofluoric acid is 3:1, The feed rate of reaction raw material 2 was 30 g / min. Raw material 1 is 20mol% fluorine-nitrogen mixed gas, and the feed rate is 5.4L / min. The molar ratio of fluorine gas to uracil is 1.2:1.

[0040] The reaction raw material 2 uracil solution enters the "heart-shaped" micro-channel reaction module 4 after passing through the micro-channel premixing and preheating module 3, and the fluorine-nitrogen mixed gas directly enters...

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Abstract

The invention discloses a method for directly fluorinating a pyrimidine derivative by using a micro-channel reactor. A uracil and/or cytosine and fluorine-containing acid and/or fluorine-containing alcohol mixture used as a raw material reacts with fluorine to prepare corresponding fluorouracil and/or fluorocytosine. The prepared fluorouracil and fluorocytosine have the advantages of high purity, low cost advantage, and safe and easily controlled fluorination process.

Description

technical field [0001] The invention relates to a method for fluorination of pyrimidine derivatives, in particular to a method for fluorination of pyrimidine derivatives using a microchannel reactor. Background technique [0002] Pyrimidine derivatives are new chemical drugs widely used in recent years, such as uracil, cytosine, thymine and so on. For example, the typical uracil compound 5-fluorouracil can be synthesized by condensation cyclization and direct fluorination. Condensation cyclization method first condenses enol sodium salt of fluoroformoacetate with urea or its derivatives to form a ring, and then performs post-treatment to obtain the corresponding product. This method has a long route, low yield, and great difficulty in product purification. . The direct fluorination method uses fluorine gas diluted with inert gas to directly react with pyrimidine derivative raw materials to obtain the target product. This method has high risk of fluorine gas resources, diff...

Claims

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Application Information

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IPC IPC(8): C07D239/47C07D239/553
CPCC07D239/47C07D239/553
Inventor 陈慧闯章祺徐卫国丁元胜
Owner ZHEJIANG RES INST OF CHEM IND CO LTD
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