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

Synthetic method of tazobactam acid

A technology for the synthesis of tazobactam acid, applied in the direction of organic chemistry, etc., can solve the problems of long synthesis process steps, many by-products, complicated process, etc., and achieve the goal of improving yield and quality, improving quality, and reducing reaction temperature Effect

Active Publication Date: 2017-08-11
SHIJIAZHUANG WANYE CHEM IND CO LTD
View PDF11 Cites 16 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The purpose of the present invention is to provide a kind of synthetic method of tazobactam, to solve the problems of long steps, complicated process, many by-products and low yield in the existing synthetic process

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
  • Synthetic method of tazobactam acid
  • Synthetic method of tazobactam acid
  • Synthetic method of tazobactam acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] The synthesis of embodiment 1 compound C

[0032] Put 300mL of water, 100mL of acetone, 21.63g (0.10mol) of 6-APA, 3.82g (0.01mol) of hexadecyltrimethylammonium bisulfate into a 1000mL four-necked bottle, stir and cool down to 0-5°C, time-consuming Add 33.81g (0.055mol) Oxone (2KHSO 5 ·KHSO 4 ·K 2 SO 4 compound salt), reacted at 0-5° C. for 2 h, and when the residual 6-APA detected by HPLC was less than 1%, the reaction was terminated to obtain compound A.

[0033] The above reaction system was cooled to -20~-10°C, 50g of hydrochloric acid with a mass fraction of 36% was added, and 26.4g of an aqueous solution of hypophosphorous acid (0.20mol of hypophosphorous acid) with a mass fraction of 50% was added dropwise. The g mass fraction is 30% sodium nitrite aqueous solution (sodium nitrite is 0.20 mol), after dripping, keep warm for 2 hours, when the remaining compound A is less than 1% as detected by HPLC, the reaction is terminated to obtain compound B.

[0034]Hea...

Embodiment 2

[0037] The synthesis of embodiment 2 compound F

[0038] Install a water separator on the 500mL four-necked bottle with a serpentine condenser, install a vacuum tube connected to the vacuum pump and a valve for adjusting the pumping volume on the upper part of the serpentine condenser, and put 200mL into the four-necked bottle Toluene, 38.35g (0.10mol) of compound C, 16.73g (0.10mol) of 2-mercaptobenzothiazole, by adjusting the pumping volume, the internal temperature is controlled at 70-80°C, and the pressure is refluxed for 3h, and the residue of compound C is detected by HPLC. 1%, end the reaction. Concentrate to dryness under reduced pressure, add 200mL tetrahydrofuran and stir to dissolve, filter off the insoluble matter, and concentrate the filtrate to dryness under reduced pressure to obtain compound D as a white foam.

[0039] Dissolve compound D in 200mL of dichloromethane, insert an ultrasonic vibrating rod into the reaction bottle, add 23.46g (0.105mol) copper brom...

Embodiment 3

[0050] The synthesis of embodiment 3 tazobactamic acid

[0051] 100mL methylene chloride, 50mL acetone, 43.45g (0.10mol) compound F, 16.33g mass fraction of 50% hydrogen peroxide (hydrogen peroxide is 0.24mol), 0.024g sodium polyphosphate (which is 50 % hydrogen peroxide weight of 0.15%), cooled to -5 ~ 0 ℃, dropwise added 24.50g (0.24mol) acetic anhydride, exothermic, temperature control 0 ~ 5 ℃, after dropping, keep warm for 4h, when HPLC detects that the compound F residue is less than 1%, end the reaction. Add 200 mL of 5% sodium sulfite aqueous solution to the reaction system, stir for 10 min, let stand to separate layers, extract the water layer with 100 mL of dichloromethane, combine the dichloromethane layers to about 300 mL, and obtain a dichloromethane solution of compound G.

[0052] Transfer the dichloromethane solution of compound G from the previous step into a 1000 mL four-necked flask, add 100 mL of methanol, cool down to -15 to -10 °C, add 100 mL of trifluoro...

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 provides a synthetic method of tazobactam acid, comprising the steps of (a) using 6-APA (6-aminopenicillanic acid) as a starting material and cetyltrimethylammonium hydrogensulfate as a catalyst to oxidize with oxone to obtain compound A; subjecting the compound A to deamination reaction to obtain compound B; esterifying the compound B to obtain compound C; (b) subjecting the compound C and 2-mercaptobenzothiazole to reduced pressure backflow to obtain compound D; ultrasonically vibrating the compound D and copper bromide to obtain compound E; reacting the compound E and 1H-1,2,3-triazole to obtain compound F; (c) allowing hydrogen peroxide and acetic anhydride to act on the compound F to obtain compound G; reacting the compound G with anisole to obtain tazobactam acid. Amino groups in 6-APA are diazotized directly, diazo groups are then removed, reduced pressure backflow and ultrasonic vibration are performed, hydrogen peroxide and acetic anhydride are used as oxidants, less byproducts are generated, and the yield and quality of tazobactam acid are effectively increased.

Description

technical field [0001] The present invention relates to a synthesis method of beta-lactamase inhibitor, in particular to a synthesis method of tazobactam. Background technique [0002] The chemical name of tazobactam acid is: (2S,3S,5R)-3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)- 4-Thio-1-azabicyclo[3.2.0]heptane-2-carboxylic acid-4,4-dioxide, molecular formula: C 10 h 12 N 4 o 5 S, molecular weight: 300.29, CAS number: 89786-04-9, the structure is as follows: [0003] [0004] Tazobactam is a new penicillane sulfone β-lactamase inhibitor developed by Japan Dapeng Pharmaceutical Company. In 1992, the compound preparation of tazobactam sodium / piperacillin sodium (1:8) was first launched in France for the treatment of various bacterial infections. Tazobactam has the characteristics of good stability, low toxicity and strong enzyme inhibitory activity, and is currently the most promising β-lactamase inhibitor in clinical evaluation. Due to the excellent properties...

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): C07D499/87C07D499/04C07D499/08
CPCC07D499/04C07D499/08C07D499/87
Inventor 李宝才潘光荣周强
Owner SHIJIAZHUANG WANYE CHEM IND CO LTD
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