Method for preparing 5-fluorouracil

A technology for fluorouracil and urea, which is applied in the field of organic chemical synthesis, can solve the problems of low yield of 5-fluorouracil, large amount of solvent used, and high production cost, and achieves the advantages of reducing the amount of solvent recovered, reducing the amount of solvent and improving the molar utilization rate. Effect

Inactive Publication Date: 2015-03-25
SHANDONG JINCHENG PHARMA & CHEM
View PDF2 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In view of the deficiencies in the prior art, the purpose of the present invention is to provide a preparation method of 5-fluoro

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] (1) In a 1000mL three-necked flask, replace with nitrogen gas, add 200g of toluene, add 45g of sodium methoxide (0.833mol) in batches, and control the temperature at 25°C; add 25g of ethyl formate dropwise, and control the dropping temperature at 5°C; 50 g of ethyl formate and 60 g of methyl fluoroacetate were added dropwise at the same time, and the dropping temperature was controlled at 10°C; after the dropwise addition, the temperature was controlled at 20°C, stirred for 1 hour, and then heated to 36°C for 5 hours.

[0026] (2) Add 65g of methanol and 30g of sodium methoxide, stir and cool down to 15°C, then add 65g of urea and react for 4h. After the reaction is complete, remove the solvent, add water, lower the temperature to 18°C, stir for 1h, adjust the pH to 3 with concentrated hydrochloric acid, and stir at 15°C for 1h; filter and wash with water to obtain 70g of the product, with a yield of 74.5% and a purity of 99.31%.

Embodiment 2

[0028] (1) In a 1000mL three-necked flask, replace it with nitrogen, add 200g of toluene, add 45g of sodium methoxide in batches, and control the temperature at 20°C; add 50g of ethyl formate dropwise, and control the dropping temperature at 10°C; then add ethyl formate 25g and 60g of methyl fluoroacetate were added dropwise at the same time, and the dropwise addition temperature was controlled at 5°C; after the dropwise addition, the temperature was controlled at 22°C, and stirred for 1h. The temperature was raised to 37°C for 8h.

[0029] (2) Add 65g of methanol and 30g of sodium methoxide, stir and cool down to 20°C, then add 65g of urea and react for 6h. After the reaction was complete, remove the solvent, then add water, lower the temperature to 10°C, stir for 2h, adjust the pH to 3.5 with concentrated hydrochloric acid, and stir at 10°C for 2h; filter and wash with water to obtain 72g of the product, with a yield of 76.6% and a purity of 99.50%.

Embodiment 3

[0031] (1) In a 1000mL three-necked flask, replace with nitrogen, add 200g of toluene, add 45g of sodium methoxide in batches, and control the temperature at 15°C; dropwise add 35g of ethyl formate, control the dropping temperature at 5°C; then add ethyl formate 40g and 60g of methyl fluoroacetate were added dropwise at the same time, and the dropwise addition temperature was controlled at 5°C; after the dropwise addition, the temperature was controlled at 25°C, and stirred for 2h. The temperature was raised to 38°C for 5h.

[0032] (2) Add 65g of methanol and 30g of sodium methoxide, stir and cool down to 25°C, then add 65g of urea to react for 4h. After the reaction was complete, remove the solvent, then add water, lower the temperature to 20°C, stir for 2h, adjust the pH to 4 with concentrated hydrochloric acid, and stir at 20°C for 2h; filter and wash with water to obtain 71g of the product, with a yield of 75.6% and a purity of 99.35%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention belongs to the field of organic chemistry synthesis and particularly relates to a method for preparing 5-fluorouracil. The method comprises the following steps: (1) after nitrogen displacement, adding sodium methoxide into toluene, then dripping part of ethyl formate at first, then dripping methyl fluoroacetate and the rest ethyl formate, and stirring after dripping for reaction; (2) adding methyl alcohol and sodium methoxide, stirring, reducing the temperature to 15-25 DEG C, adding urea for reaction, removing a solvent after reaction, re-adding water, cooling, stirring, regulating the pH to 3-4, and filtering to obtain the product. According to the invention, as ethyl formate and methyl fluoroacetate are mixed and dripped, and the dripping temperature is reduced, loss of ethyl formate is reduced, accordingly, reaction of ethyl formate and methyl fluoroacetate is promoted, and the yield is improved to be more than 74.5%; addition of the solvent is reduced, so that the solvent reclamation amount can be remarkably reduced and the manufacturing cost is greatly lowered.

Description

technical field [0001] The invention belongs to the field of organic chemical synthesis, and in particular relates to a preparation method of 5-fluorouracil. Background technique [0002] In addition to being an antibacterial drug itself, 5-fluorouracil is also the main intermediate for the preparation of anticancer drugs such as capecitabine. Therefore, 5-fluorouracil has a broad market prospect, and the development of a more environmentally friendly and lower-cost new process has extremely great practical significance for the wide application of 5-fluorouracil. [0003] Patent 201310343187.0 relates to the preparation process of 5-fluorouracil involved in step a of the 5-fluorouracil preparation process: add sodium methoxide to toluene in batches, after the addition, ethyl formate is added dropwise, and then methyl fluoroacetate is added dropwise Esters, after dripping and stirring for 1.0-2.0h, heat up to 36-38°C and react for 5-8h; then add methanol and sodium methoxide...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D239/553
CPCC07D239/553
Inventor 李珊珊孙智源赵奇叶德坤张德仕
Owner SHANDONG JINCHENG PHARMA & CHEM
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap