Synthesis method for dextrorotation cefamandole nafate

A technology of cefamandole sodium and its synthetic method, which is applied in the direction of organic chemistry, can solve problems such as difficult methods, complicated treatment, high toxicity, etc., and achieve the effects of easy-to-obtain raw materials, simple operation methods, and low cost

Active Publication Date: 2017-04-19
哈药集团股份有限公司 +1
View PDF9 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Chinese patent CN 102372728A only introduces the preparation of a synthetic intermediate 7-amino-3-[(1-methyl-1H-tetraza-5-yl)mercaptomethyl]-3-cephem-4-carboxylic acid method, using boron trifluoride as a catalyst, condensing 7-ACA and methylmercapto tetrazolium in an organic solvent, which is also a commonly used method now, but its disadvantage is that the solvent is a second-class solvent or a first-class solvent with high toxicity , and the post-processing is also more complicated
[0012] At present, there are no reports about the synthesis of dextro-cefamandal acid. Occasionally seeing dextro-cefamando-acetic acid on the market is only obtained by separation. Low

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
  • Synthesis method for dextrorotation cefamandole nafate
  • Synthesis method for dextrorotation cefamandole nafate
  • Synthesis method for dextrorotation cefamandole nafate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1 Preparation of 7-ATCA

[0041] Add 43.5g of acetonitrile, 7.1g of mercaptotetrazolium, 16g of 7-ACA into the four-neck flask, stir evenly, and add BF within 15 minutes 3 - 63g of acetonitrile, raise the inner temperature to 35~39°C, react with stirring for 50~60 minutes, and cool to the inner temperature of 28~32°C. Add (14.76g hydrochloric acid + 12.6g water) mixed solution within 15 minutes, keep the temperature, stir for 40 minutes, cool down to 10~20°C, and grow the crystal for 1 hour. Suction filtration, top washing with 120ml of acetone in 4 times. Vacuum dry at 45°C for 15 hours. (Moisture content ≤ 1.0% before unloading) 19.5 g of solid was obtained, with a molar yield of 95.1% and a purity of 99.9%.

Embodiment 2

[0042] Example 2 Preparation of 7-ATCA

[0043] Add 43.5g of dimethyl carbonate, 7.1g of mercaptotetrazolium, 16g of 7-ACA into the four-necked bottle, stir well, and add BF within 15 minutes 3 - Dimethyl carbonate 63g, raise the inner temperature to 35~39°C, react under stirring for 50~60 minutes, then cool to the inner temperature of 28~32°C. Add (14.76g hydrochloric acid + 12.6g water) mixed solution within 15 minutes, keep the temperature, stir for 40 minutes, cool down to 10~20°C, and grow the crystal for 1 hour. Suction filtration, top washing with 120ml of acetone in 4 times. Vacuum dry at 45°C for 15 hours. 19.5 g of solid was obtained, the molar yield was 95.1%, and the purity was 99.9%.

Embodiment 3

[0044] Example 3 Preparation of Dextrocefamandol Sodium

[0045] Add 175ml of ethyl acetate into the four-necked bottle, add 19g of the first-step product 7-ATCA under stirring, add 8.76g of trimethylchlorosilane and 11.37g of hexamethyldisilazane, raise the internal temperature to 54~56°C, and react 80~90 minutes. After the reaction, cool down to 28~32°C, add 5.6g of acetamide, continue cooling down to -5~-10°C, add 11.83g of S-(-)-formylated mandelic acid chloride (internal temperature ≤ 2°C). Maintain the internal temperature at -2~-7°C for 15~30 minutes, add 115ml of water at 2~4°C (internal temperature ≤4°C), maintain the internal temperature for 15~25 minutes, raise the temperature to 10°C, separate the phases, and discard the water phase , and the ester phase was transferred to another four-necked bottle. Add 350ml of isopropanol and raise the temperature to 20~25°C.

[0046] Add the prepared acetone / sodium isooctanoate solution (104g / 10g) into the four-necked bottle...

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 synthesis method for dextrorotation cefamandole nafate. The method includes the steps that in one-element organic solvent, 7-ACA and 1-methyl-1h-tetrazole-5-thiol are subjected to condensation with a boron trifluoride complex of the one-element organic solvent as a catalyst so as to generate 7-ATCA; and then, in another one-element organic solvent, under the effect of organic alkali, the 7-ATCA and S-(-)-formylmandeloyl chloride are made to react so as to generate the dextrorotation cefamandole nafate, then, an organic phase is left after hydrolysis and extraction phase splitting, organic acid sodium salt and another organic solvent indissolvable in dextrorotation cefamandole sodium are added, the dextrorotation cefamandole sodium is obtained through crystallization, finally, the dextrorotation cefamandole sodium is dissolved in water, organic solvent incapable of being dissolved in water is added together with organic or inorganic acid, an organic phase is left after extraction phase splitting, and reduced pressure rotary evaporation is conducted on the organic phase to obtain the dextrorotation cefamandole nafate. The method is simple, conditions are gentle, raw materials are easy to obtain, and purity of the finally-obtained product is 99% or above.

Description

technical field [0001] The invention relates to the field of pharmaceutical synthesis, in particular to a method for synthesizing D-cefamandolic acid. Background technique [0002] The English name of cefamandolic acid is Cefamandomle Nafate, the chemical name is (6R, 7R)-7(R)-(2-formyloxy-2-phenylacetamido]-3[[(1-methyl-1H- Tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, the product is from the United States The chemical structural formula of the second-generation cephalosporin antibiotics originally developed by mlimlmly is shown in the following formula (I): [0003] [0004] (I) [0005] Cefamandole sodium is the second-generation cephalosporin antibiotics. The antibacterial activity of cefamandole sodium is only 1 / 5 of that of cefamandole. Cefamandole sodium enters the body and is rapidly hydrolyzed into cefamandole. Therefore, both The antibacterial effect in the body is basically the same. Cefamandole has a strong antibac...

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): C07D501/36C07D501/06
CPCC07D501/06C07D501/36
Inventor 赵玉新谢英新王喜军石成
Owner 哈药集团股份有限公司
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