Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Tazobactam synthesis method

A technology for tazobactam and a synthesis method, which is applied in the field of synthesis of β-lactamase inhibitor tazobactam, can solve the problems of danger and explosion, low total yield and the like, and achieves easy operation, mild reaction conditions, The effect of easy industrial production

Active Publication Date: 2013-04-03
YIYUAN XINQUAN CHEM
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The advantage of this process is that penicillin G potassium salt is much cheaper than 6-aminopenicillanic acid. The disadvantage is that it uses dangerous and explosive substances and generates six-membered cycloisomerization by-products in the nucleophilic substitution reaction. low overall yield

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
  • Tazobactam synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] (1) Add CH to a 1000mL three-necked bottle 2 Cl 2 300mL and 1.5mol.L -1 h 2 SO 4 100mL, stirred and cooled to 0°C, then added 36.5g (0.228mol) of bromine, 0.33g of hexadecyltrimethylammonium bromide and 10.5g (0.152mol) of sodium nitrite into the reaction liquid, and continued stirring to dissolve Then add 33g (0.152mol) of 6-APA in batches, and after stirring for 1h at 0-5°C, add 1mol.L -1 NaHSO 3 Until the solution is tested with KI-starch test paper and does not change color. Then let the layers stand, and the water layer was washed with 100mL CH 2 Cl 2 After two extractions, the organic layers were combined, followed by water, 7% NaHCO 3 Aqueous solution, saturated sodium chloride aqueous solution washing, the obtained CH containing 6,6-dibromopenicillanic acid 2 Cl 2 The solution was directly used in the next reaction.

[0062] (2) Add CH of 6,6-dibromopenicillanic acid in a 1000mL three-necked bottle 2 Cl 2 Solution (about 400ml), after cooling down ...

Embodiment 2

[0070] (1) Add CH to a 1000mL three-necked bottle 2 Cl 2 300mL and 1.5mol.L -1 h 2 SO 4 100mL, stirred and cooled to 0°C, then added 73g (0.456mol) of bromine, 1.65g of hexadecyltriethylammonium bromide and 10.5g (0.152mol) of sodium nitrite into the reaction liquid, and kept stirring, after dissolving Add 33g (0.152mol) of 6-APA in batches, and after stirring for 1h at 0-5°C, add 1mol.L -1 NaHSO 3 Until the solution is tested with KI-starch test paper and does not change color. Then let the layers stand, and the water layer was washed with 100mLCH 2 Cl 2 After two extractions, the organic layers were combined, followed by water, 7% NaHCO 3 Aqueous solution, saturated sodium chloride aqueous solution washing, the obtained CH containing 6,6-dibromopenicillanic acid 2 Cl 2 The solution was directly used in the next reaction.

[0071] (2) Add CH of 6,6-dibromopenicillanic acid in a 1000mL three-necked bottle 2Cl 2 Solution (about 400ml), after cooling down to 5°C,...

Embodiment 3

[0078] (1) Add CH to a 1000mL three-necked bottle 2 Cl 2 300mL and 1.5mol.L -1 h 2 SO 4 100mL, stirred and cooled to 0°C, then added 122g (0.762mol) of bromine, 2.2g of dodecyltrimethylammonium bromide and 35g (0.508mol) of sodium nitrite into the reaction solution, and kept stirring, dissolved and divided Add 55g (0.254mol) of 6-APA in batches, and after stirring for 1h at 0-5°C, add 1mol.L -1 NaHSO 3 Until the solution is tested with KI-starch test paper and does not change color. Then let the layers stand, and the water layer was washed with 100mL CH 2 Cl 2 After two extractions, the organic layers were combined, followed by water, 7% NaHCO 3 Aqueous solution, saturated sodium chloride aqueous solution washing, the obtained CH containing 6,6-dibromopenicillanic acid 2 Cl 2 The solution was directly used in the next reaction.

[0079] (2) Add CH of 6,6-dibromopenicillanic acid in a 1000mL three-necked bottle 2 Cl 2 Solution (about 400ml), after cooling down to ...

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 a tazobactam synthesis method which comprises the steps of: with 6-APA(Amino Penicillanic Acid) as raw material, preparing a key intermediate 6,6-dihydro penam sulphoxide acid diphenylcarbinol ester through successive reactions of esterification, oxidation, reduetive debromination and the like without separation; then, reacting with 2-triphenyl silicon-1,2,3-triazole; introducing a triazole ring; and finally obtaining the final product of tazobactam through potassium permanganate oxidation and metacresol deprotection. The tazobactam synthesis method is mainly characterized in that a phase transfer catalyst is introduced in the first step, therefore, the reaction rate and the product purity are improved; since an environment-friendly hydrogen peroxide-cobalt acetate catalytic oxidation system is adopted in the third step, the characteristics of good reaction selectivity, high yield, catalyst recyclability and the like are achieved; a method for synthesizing 2 alpha-methyl-2 beta-(1,2,3- triazole-1- radical) methyl penam-3 alpha-carboxylic acid diphenylcarbinol ester by using 2-triphenyl silicon-1,2,3-triazole is adopted in the fifth step, and the tazobactamsynthesis method is simple and convenient to operate, is safe and reliable, shortens the reaction route and improves the total yield. Compared with the traditional process, the tazobactam synthesis method greatly reduces the production cost and the environment pollution and has greater implementation value and economic benefits.

Description

technical field [0001] The invention relates to a method for synthesizing beta-lactamase inhibitor tazobactam. Background technique [0002] Tazobactam, chemical name (2S,3S,5R)-3-methyl-7-oxo-3-(1H-1,2,3,-triazolylmethyl]-4-thia-1 -Azabicyclo[3.2.0]heptane-2-carboxylic acid-4,4-dioxide.It is a β-lactamase inhibitor developed by Japan Dapeng Pharmaceutical Company, which has low toxicity, good stability, It has the characteristics of strong enzyme inhibitory activity, and has achieved extremely effective synergistic effects when combined with ampicillin, amoxicillin, piperacillin and other antibiotics. It is an important pharmaceutical intermediate. [0003] According to the different starting materials, there are three main synthetic routes of tazobactam. [0004] Taniguchi, M. et al. (EP 0331146,1989) etc. use penicillane-3α carboxylate diphenylmethyl ester-1β-oxide as raw material [0005] Tazobactam was synthesized by ring opening, chloromethylation, azidation, potass...

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): C07D499/87C07D499/08
CPCY02P20/584
Inventor 鲜树雍高峰张立明翟风陈坤李学平李祥伟
Owner YIYUAN XINQUAN CHEM
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com