Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of improved preparation technology of cefmetazole intermediate

A technique for preparing cefmetazole and its preparation process, which is applied in the field of improved preparation process of cephalosporin compound intermediates, can solve the problems of large amount of silanization reagents, heavy environmental pollution, and high single-step cost, and achieve single-step cost reduction and pollution reduction , Yield and Purity Improvement

Active Publication Date: 2021-03-12
CHONGQING CHANGJIE MEDICINE CHEM +1
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] The defect of this prior preparation technology is that the silylating reagent is a fuming reagent, which is highly toxic and causes serious environmental pollution.
And the amount of silanization reagent is large, far exceeding the theoretical amount, and the single-step cost is high
[0016] The key intermediate IV has a wide range of uses. The existing preparation technology uses silanization reagents, which have defects such as high toxicity, heavy environmental pollution, large dosage, and high single-step cost. Improving and optimizing the preparation process of this step has become an urgent technical problem in this field.

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

[0036] Intermediate III (by feeding 25 g of intermediate I, intermediate III prepared by the method described in Test Example 1) was dissolved in 400 ml of ethyl acetate, and dry HCl gas was passed into the reaction liquid, and the temperature was slowly raised to 40 ° C, and kept React at 40°C until the reaction is complete (1.5~2h), stop the reaction, cool the reaction to -20°C, add 300ml of ice water, 100ml of ethyl acetate, stir at 8-10°C for 30min, separate layers, and extract the water layer with ethyl acetate When there is no product, combine the organic layers, wash with saturated brine, dry, filter with suction, wash the filter cake with ethyl acetate, and concentrate the filtrate to dryness at 5~10°C to obtain oily intermediate IV with a yield of 94% and a purity of 96 %.

Embodiment 2

[0038] Intermediate III (25 g of Intermediate I, prepared by the method described in Test Example 1) was dissolved in 400 ml of ethyl acetate, and 46 ml of dry 2N HCl ethyl acetate solution was passed into the reaction solution (phase Ratio to intermediate III molar equivalent is 2.0eq), slowly heat up to 40°C, keep at 40°C until the reaction is complete (1.5~2h), stop the reaction, cool the reaction to -20°C, add 300ml of ice water, 100ml of ethyl acetate , stirred at 8-10°C for 30 minutes, separated layers, extracted the aqueous layer with ethyl acetate until no product was found, combined the organic layers, washed with saturated brine, dried, and suction filtered, the filter cake was washed with ethyl acetate, and the filtrate was separated in 5~ Concentrate to dryness at 10°C to obtain oily intermediate IV with a yield of 95% and a purity of 95.5%.

Embodiment 3

[0040] Intermediate III (25 g of intermediate I, prepared by the method described in Test Example 1) was dissolved in 400 ml of ethyl acetate, and 207 ml of dry 2N HCl ethyl acetate solution was passed into the reaction solution (phase Ratio to intermediate III molar equivalent is 9.0eq), slowly heat up to 40°C, keep at 40°C until the reaction is complete (1.5~2h), stop the reaction, cool the reaction to -20°C, add 300ml of ice water, 100ml of ethyl acetate , stirred at 8-10°C for 30 minutes, separated layers, extracted the aqueous layer with ethyl acetate until no product was found, combined the organic layers, washed with saturated brine, dried, and suction filtered, the filter cake was washed with ethyl acetate, and the filtrate was separated in 5~ Concentrate to dryness at 10°C to obtain oily intermediate IV with a yield of 93.7% and a purity of 96.5%.

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 relates to an improved preparation process of a cefmetazole intermediate (intermediate IV). In the method, a protonic acid is used in a suitable solvent to replace the silylating reagent in the prior art to prepare the intermediate IV from the intermediate III, the conversion rate is increased to 98%, and the single-step yield is 90-95%. The improved preparation process disclosed in the present invention avoids the hazards of silylating reagent fumes to technicians and the pollution to the environment; and the protonic acid used in the present invention is cheap and easy to obtain, the reaction conditions are mild, and the single-step cost is greatly reduced; the intermediate preparation The intermediate IV can be directly used in the next step reaction without post-treatment purification, or the intermediate IV can be prepared into a salt according to the existing salt-forming technology for industrial application.

Description

technical field [0001] The invention belongs to the field of drug synthesis and preparation, and in particular relates to an improved preparation process of cephalosporin compound intermediates. Background technique [0002] Cefmetazole sodium, chemical name: (6R,7S)-7-[[2-(cyanomethylthio)acetyl]amino]-7-methoxy-3-[(1-methyltetrazole-5 -yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt, the molecular formula is: C 15 h 16 N 7 NaO 5 S 3 , the structural formula is as follows: [0003] . [0004] Cefmetazole sodium is a second-generation cephalosporin, a semi-synthetic cephalosporin antibiotic created by Japan Sankyo Company, which has good stability to the broad-spectrum β-lactamase produced by negative bacilli. Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Shigella, Salmonella, Staphylococcus aureus, group A hemolytic streptococcus, and Brahamella catarrh are all sensitive to this product. Clinically, it is mainly...

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 Patents(China)
IPC IPC(8): C07D501/57C07D501/04
CPCC07D501/04C07D501/57
Inventor 曾秀秀白江燕
Owner CHONGQING CHANGJIE MEDICINE CHEM