Method for synthesizing meropenem side chain intermediate thiol lactone by using sodium hydrosulfide

A meropenem side chain and sodium hydrosulfide technology, applied in the field of chemical substance preparation, can solve problems affecting the health and safety of operators, increase the cost of personnel and equipment, and unfavorable green production of enterprises, so as to achieve healthy work and easy The effect of mild storage and reaction conditions

Inactive Publication Date: 2020-08-28
TIANJIN UNIV
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The sodium sulfide used in this process is easy to deliquesce in the air, and will be carbonized and deteriorated. The storage requirements are high. The aqueous solution of sodium sulfide is easily oxidized into sodium thiosulfate, sodium sulfite, sodium sulfate and sodium polysulfide. It is unstable in nature and continuously emits sulfide Hydrogen gas is difficult to recover, the environment is polluted, and the operating environment is dangerous, which affects the health and safety of operators, is not conducive to the green production of enterprises, and increases the cost of personnel and equipment to a certain extent. Therefore, it is urgent to find a vulcanization with stable chemical properties. Substitute for the synthesis of thiol lactones from sodium sulfide

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
  • Method for synthesizing meropenem side chain intermediate thiol lactone by using sodium hydrosulfide
  • Method for synthesizing meropenem side chain intermediate thiol lactone by using sodium hydrosulfide
  • Method for synthesizing meropenem side chain intermediate thiol lactone by using sodium hydrosulfide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] 1) Add 1.8 g of M1 (ie, [(2S,4R)-2-carboxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine)] to 32 mL of dichloromethane, keep the liquid temperature at -16°C, First add 0.71g isopropyl chloroformate dropwise, then add 0.76g TEA dropwise, and react for 15 minutes;

[0024] 2) Add 0.86g MsCl dropwise at -16°C, then add 0.70g TEA dropwise, and react for 26min;

[0025] 3) Dissolve 1.81g NaHS, 0.24g PEG-600 and 1.74g water into a solution, add this solution into the reaction mixture solution at -16°C, raise the temperature from -16°C to 0°C, and keep the heating time for 25min; , Add 8 mL of deionized water at 0°C for liquid separation. The organic phase was separated, and the temperature of the organic phase was raised to 40° C. for reflux reaction. The reflux reaction time was 2.5 hours. After the reaction was completed, a thiol lactone solution was obtained;

Embodiment 2

[0028] 1) Add 1.8g M1 to 33mL dichloromethane, keep the liquid temperature at -15°C, add 0.71g isopropyl chloroformate dropwise, then add 0.77g TEA dropwise, and react for 14min;

[0029] 2) Add 0.85g MsCl dropwise at -15°C, then add 0.71g TEA dropwise, and react for 25min;

[0030] 3) Dissolve 1.67g NaHS, 0.25g PEG-2000 and 1.74g water into a solution, add this solution into the reaction solution at -15°C, raise the temperature from -15°C to 0°C, and keep the heating time for 26min; after the heating is completed, Add 9 mL of deionized water at 0°C for liquid separation, separate the organic phase, raise the temperature of the organic phase to 39°C for reflux reaction, and reflux for 3 hours. After the reaction is completed, a thiol lactone solution is obtained;

[0031] 4) Post-treat the obtained thiol lactone solution, add 6% potassium carbonate solution at 1°C to adjust to pH=8, separate oil phase 1, and continue to adjust oil phase 1 to 1 at 1°C with 19% hydrochloric acid...

Embodiment 3

[0033] 1) Add 1.8g M1 to 33.5mL dichloromethane, keep the liquid temperature at -16°C, first add 0.72g isopropyl chloroformate dropwise, then add 0.77g TEA dropwise, and react for 12 minutes;

[0034] 2) Add 0.86g MsCl dropwise at -16°C, then add 0.72g TEA dropwise, and react for 26min;

[0035] 3) Dissolve 1.95g NaHS, 0.26g PEG-600 and 1.74g water into a solution, add this solution into the reaction solution at -16°C, raise the temperature from -16°C to 0°C, and keep the heating time for 25min; after the heating is completed, Add 10 mL of deionized water at 0°C for liquid separation, separate the organic phase, raise the temperature of the organic phase to 38°C for reflux reaction, and reflux for 2.8 hours. After the reaction is completed, a thiol lactone solution is obtained;

[0036] 4) Post-treat the obtained thiol lactone solution, add 5% potassium carbonate solution at 0°C to adjust to pH=8.5, separate the oil phase 1, and continue to adjust the oil phase 1 to 0 with 17%...

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 method for synthesizing meropenem side chain intermediate thiol lactone by using sodium hydrosulfide. The thiol lactone is synthesized by performing carboxyl activation andhydroxyl activation on a reactant M1 and adding polyethylene glycol and sodium hydrosulfide through a one-pot method. The thiol lactone is synthesized by performing carboxyl activation and hydroxyl activation on the M1 and adding the PEG and NaHS through one-pot vulcanization and cyclization, the conversion rate of the M1 is obviously improved; the highest yield of the thiol lactone is 98.9 percent or higher; the purity reaches 97.4 percent or higher; reaction conditions are mild and safe. The adopted sodium hydrosulfide is stable in chemical property and easy to store; the synthesized thiol lactone is high in yield; the defects that sodium sulfide is easy to deliquesce and oxidize, high in toxicity, unstable in property, high in storage requirement and the like are overcome, environmentalpollution is reduced, the operation environment is safe, healthy work of experimenters is facilitated, the cost of personnel and equipment is reduced to a certain extent, and the method is suitable for green and efficient large-scale production of enterprises.

Description

technical field [0001] The invention relates to the technical field of chemical substance preparation, in particular to a method for synthesizing meropenem side chain intermediate thiolactone by using sodium hydrosulfide. Background technique [0002] Meropenem is the second-generation carbapenem antibiotic and the first carbapenem antibiotic that can be used alone. Antibacterial, it shows good effect on the treatment of respiratory system infection caused by bacterial infection. [0003] At present, meropenem is mainly prepared by chemical total synthesis. The main synthesis process includes the synthesis of meropenem side chains, the synthesis of the skeleton mother nucleus, and the reaction of the meropenem side chain with the skeleton mother nucleus to obtain meropenem. Among them, the meropenem side chain is the most important One of the key factors for the yield of meropenem. [0004] The main potential synthesis method of the meropenem side chain is the thiol lacton...

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 Applications(China)
IPC IPC(8): C07D495/08
CPCC07D495/08
Inventor 李彬史继星姜爽张天永
Owner TIANJIN UNIV
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