New preparation method of ceftiofur sodium

A technology for ceftiofur sodium and ceftiofur, which is applied in the direction of organic chemistry and the like, can solve the problems of product purity and solubility that cannot meet medicinal requirements, and the cost is difficult to control, and achieves shortened synthesis steps, low cost and simplified operation. effect of the program

Inactive Publication Date: 2015-04-22
HENAN LINGXIAN SCI & TECHN PHARMA
View PDF4 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The advantage of this method is that the purity is guaranteed and the yield is relatively high, but the cost is difficult to control, and the purity and solubility of the product cannot meet the requirements of medicine

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

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • New preparation method of ceftiofur sodium
  • New preparation method of ceftiofur sodium
  • New preparation method of ceftiofur sodium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] (1) Synthesis of intermediate (I) 2-furan methylthiol acid

[0029] Add 150 mL of distilled water to a clean 250 mL three-neck reaction flask equipped with a stirrer and a thermometer, then weigh 15.0 g (about 0.26 mol) of sodium hydrogen sulfide (NaHS), keep stirring and control the temperature at 25-27 °C Slowly add 25 mL (about 30 g, 0.23 mol) of furoyl chloride (furoyl chloride), keep stirring, and keep the temperature at 25-27 °C for 1 h. During this period, use 10% sodium hydroxide solution to adjust the pH at About 7.0, after the reaction is complete, use 10% hydrochloric acid to adjust the pH to about 1.5-2.0, cool to 5 ℃, crystallize for 1 h, filter under reduced pressure, wash with appropriate amount of water, get a light yellow solid by suction filtration, recrystallize with acetonitrile, and dry in vacuo 27 g of intermediate (I) was obtained.

[0030] (2) Synthesis of intermediate (II) 7-amino-3-[(2-furyl-carbonyl)-thiomethyl]-3-cephem-4-carboxylic acid

...

Embodiment 2

[0036] (1) Synthesis of intermediate (I) 2-furan methylthiol acid

[0037] Add 150 mL of distilled water to a clean 250 mL three-neck reaction flask equipped with a stirrer and a thermometer, then weigh 15.0 g (about 0.26 mol) of sodium hydrogen sulfide (NaHS), keep stirring and control the temperature at 25-27 °C Slowly add 25 mL (about 30 g, 0.23 mol) of furoyl chloride (furoyl chloride), keep stirring, and keep the temperature at 25-27 °C for 1 h. During this period, use 10% sodium hydroxide solution to adjust the pH at About 7.0, after the reaction is complete, use 10% hydrochloric acid to adjust the pH to about 1.5-2.0, cool to 5 ℃, crystallize for 1 h, filter under reduced pressure, wash with appropriate amount of water, get a light yellow solid by suction filtration, recrystallize with acetonitrile, and dry in vacuo 26.7 g of intermediate (I) was obtained.

[0038] (2) Synthesis of intermediate (II) 7-amino-3-[(2-furyl-carbonyl)-thiomethyl]-3-cephem-4-carboxylic acid ...

Embodiment 3

[0044] (1) Synthesis of intermediate (I) 2-furan methylthiol acid

[0045] Add 150 mL of distilled water to a clean 250 mL three-neck reaction flask equipped with a stirrer and a thermometer, then weigh 15.0 g (about 0.26 mol) of sodium hydrogen sulfide (NaHS), keep stirring and control the temperature at 25-27 °C Slowly add 25 mL (about 30 g, 0.23 mol) of furoyl chloride (furoyl chloride), keep stirring, and keep the temperature at 25-27 °C for 1 h. During this period, use 10% sodium hydroxide solution to adjust the pH at About 7.0, after the reaction is complete, use 10% hydrochloric acid to adjust the pH to about 1.5-2.0, cool to 5 ℃, crystallize for 1 h, filter under reduced pressure, wash with appropriate amount of water, get a light yellow solid by suction filtration, recrystallize with acetonitrile, and dry in vacuo 28.2 g of intermediate (I) was obtained.

[0046] (2) Synthesis of intermediate (II) 7-amino-3-[(2-furyl-carbonyl)-thiomethyl]-3-cephem-4-carboxylic acid ...

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 discloses a new preparation method of ceftiofur sodium. The method comprises the following steps: synthesizing 2-furylcarbothiolic acid and sodium hydrosulfide, synthesizing 7-amino-3-[(2-furyl-carbonyl)-sulfomethyl]-3-cephem-4-carboxylic acid from 7-ACA and 2-furylcarbothiolic acid in a boron trifluoride ether complex and acetonitrile, reacting 7-amino-3-[(2-furyl-carbonyl)-sulfomethyl]-3-cephem-4-carboxylic acid with AE-active ester, and directly reacting the obtained substance with sodium iso-octoate to obtain ceftiofur sodium. The method shortens synthesis step and simplifies the operating process, so the method has the advantages of cheap and easily available raw materials and reagents, simple operation, environmental protection, high yield, low cost, and suitableness for industrial production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, in particular to the preparation of a veterinary antibiotic, in particular to a new preparation method of ceftiofur sodium. Background technique [0002] With the development of modern animal husbandry, the long-term abuse of antibiotics in the past has led to the emergence of drug resistance and drug residues in many bacteria, which has attracted more and more attention. In particular, the large-scale outbreak of bird flu in recent years has caused the entire pharmaceutical industry to think deeply about medication. [0003] Ceftiofur sodium is the third-generation cephalosporin veterinary drug successfully developed by Upjohn Company in the 1980s. Its chemical name is (6R, 7R)-7-[2-(2-aminothiazol-4-yl)- (Z)-2-(Methoxyimino)acetamido]-3-[(2-furylcarbonyl)thiomethyl]-3-cephem-4-carboxylate sodium, which is usually treated with cefotaxime Furic acid and sodium salt synthesis. Its mechanism o...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/04C07D501/06
CPCC07D501/36C07D501/04C07D501/06
Inventor 刘裕东贺国超郭有钢刘占领
Owner HENAN LINGXIAN SCI & TECHN PHARMA
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