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

Process of synthesizing (2S-trans)-3-methyl-4-oxo-1-azacyclo butyl sulfonic acid

A technology of azetidine sulfonic acid and sulfamic acid, which is applied in the direction of organic chemistry, can solve the problems of difficult operation and low yield, and achieve the effects of low cost, increased yield, and simple process operation

Active Publication Date: 2007-06-06
CHINA RESOURCES SAIKE PHARMA
View PDF4 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] The operational route of synthetic (2S-trans)-3-amino-2-methyl-4-oxo-1-azetidinesulfonic acid all involves the step of sulfonation on the amino group, and the yield of this step is relatively low, And use extremely toxic chlorosulfonic acid, it is not easy to operate in industrialization

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
  • Process of synthesizing (2S-trans)-3-methyl-4-oxo-1-azacyclo butyl sulfonic acid
  • Process of synthesizing (2S-trans)-3-methyl-4-oxo-1-azacyclo butyl sulfonic acid
  • Process of synthesizing (2S-trans)-3-methyl-4-oxo-1-azacyclo butyl sulfonic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Step A:

[0060] In a 2L three-necked flask, add 350ml of water and 350ml of 1,4-dioxane, stir evenly, add 67.3g of L-threonine, 94.5ml of triethylamine, and 181g of di-tert-butyl dicarbonate, react overnight at room temperature, point After the plate reaction is complete, add 500ml of ethyl acetate, stir for 30 minutes, remove the organic layer, adjust the pH of the aqueous layer to 2-3 with hydrochloric acid, extract with ethyl acetate 300×3, combine the organic layers, and dry with anhydrous sodium sulfate. Filtration and concentration gave 115 g of a colorless oily substance with a yield of 93%.

[0061] Step B

[0062] Take 11.2g of the product of step A and dissolve it in a 250ml three-neck flask with 100ml of tetrahydrofuran, cool to -5°C with an ice-salt bath, add 7.2g of 1-hydroxybenzotriazole, and add 11.7g of N,N-dicyclohexylcarbodiimide , stirred for 30 minutes, added 5.5g sulfamic acid and 5.7g triethylamine, reacted at low temperature for 1 hour, removed...

Embodiment 2

[0070] Step A:

[0071] In a 2L three-necked flask, add 350ml of water and 350ml of 1,4-dioxane, stir well, add 67.3g of L-threonine, 94.5ml of triethylamine, dropwise add 144g of benzyl chloroformate, after the dropwise addition, React overnight at room temperature, after the plate reaction is complete, add 500ml of ethyl acetate, stir for 30 minutes, remove the organic layer, adjust the pH of the aqueous layer to 2-3 with hydrochloric acid, extract with ethyl acetate 300×3, combine the organic layers, and use Dry over sodium sulfate, filter, and concentrate to obtain 136 g of a colorless oil, with a yield of 95%.

[0072] Step B

[0073] Take 13g of the product of step A and dissolve it in a 250ml three-necked flask with 100ml of tetrahydrofuran, cool it to -5°C with an ice-salt bath, add 7.2gl-hydroxybenzotriazole, add 11.7g of N,N-dicyclohexylcarbodiimide, Stir for 30 minutes, add 5.5g sulfamic acid and 5.7g triethylamine, react at low temperature for 1 hour, remove the ...

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 present invention relates to process of synthesizing (2S-trans)-3-amino-2-methyl-4-oxo-1-azacyclo butyl sulfonic acid. The process includes the following steps: 1. reaction of L-threonine and matter to protect its amino group; 2 condensation of L-threonine with protected amino group and aminosulfonic acid to obtain threonyl aminosulfonic acid with protected amino group; 3. reaction of threonyl aminosulfonic acid with protected amino group and methylsulfnyl chloride to protect hydroxyl radicap in threonine segment; 4. cyclization reaction to form protected quaternary ammonium salt of azacyclo butyl sulfonic acid; and 5. deprotection to obtain (2S-trans)-3-amino-2-methyl-4-oxo-1-azacyclo butyl sulfonic acid.

Description

Technical field: [0001] The invention relates to a new method for synthesizing (2S-trans)-3-amino-2-methyl-4-oxo-1-azetidinesulfonic acid. Background technique: [0002] (2S-trans)-3-amino-2-methyl-4-oxo-1-azetidinesulfonic acid is a key intermediate in the synthesis of aztreonam. Aztreonam is an antibacterial drug developed by Bristol-Myers Squibb Company of the United States. It was launched in Italy in 1984. It is a monocyclic β-lactam antibiotic that can be synthesized artificially. The antimicrobial spectrum mainly includes Gram-negative bacteria, such as Escherichia coli, Klebsiella, Serratia, Proteus mirabilis, Haemophilus influenzae, Citrobacter, Pseudomonas aeruginosa, Neisseria gonorrhoeae, etc. It is mainly used clinically for respiratory tract, lung infection, urinary tract infection, abdominal infection, bone and joint infection, skin and soft tissue inflammation, gynecological infection, and gonorrhea caused by sensitive Gram-negative bacteria. Because this p...

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): C07D205/08
Inventor 杨琰刘亚杰
Owner CHINA RESOURCES SAIKE PHARMA
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