Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Preparation method of meropenem

A single technology of meropenem, which is applied in the field of preparation of carbapenem compound meropenem, can solve the problems of fast reaction speed, poor product purity, and many degradation products, and achieve the effect of reducing product degradation and improving product purity

Inactive Publication Date: 2012-10-17
CSPC ZHONGQI PHARM TECH (SHIJIAZHUANG) CO LTD
View PDF6 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] Although this method no longer needs to be divided into equal steps in the post-treatment process, since the raw material meropenem intermediate 2 used in the reaction and the resulting product meropenem are still dissolved in the reaction solution, the reaction speed is fast, there are many degradation products, and the product purity is poor. and because the reaction still needs to use an organic solvent, there is also the disadvantage of using the organic solvent mentioned by CN1995040A
[0015] Subsequent documents such as CN101410398A, CN101348466A, CN101935321A, etc. have also reported the similar methods of CN1995040A and CN1948312A. Although buffer salts are no longer used in the reaction, a mixture of water and organic solvents (including water-soluble and water-insoluble organic solvents) is still used. Solvent is as reaction medium, so still there is the disadvantage described in CN1995040A disclosed method

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
  • Preparation method of meropenem
  • Preparation method of meropenem
  • Preparation method of meropenem

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: Preparation of Meropenem Trihydrate

[0035] 40.0 L of deionized water, 21.0 Kg (1.43 mol) of meropenem intermediate, 0.46 L (3.97 mol) of 2,6-lutidine, and 0.5 Kg of 10% palladium on carbon were sequentially added into a 100 L hydrogenation reactor. Nitrogen was replaced several times, hydrogen was replaced several times, and finally hydrogen was passed to the pressure of 1.0 MPa in the kettle, the temperature was controlled at 30°C, and stirred for 3 hours. Stirring was stopped, hydrogen was discharged and replaced with nitrogen. Filter and recover the filter cake for reuse; add 160L of acetone to the filtrate, stir and crystallize at 10°C for 4h. After filtration and vacuum drying, 0.425 Kg of off-white solid was obtained, the molar yield was 67.8%, the HPLC purity was 99.4%, and the heavy metal content was less than 10 ppm.

Embodiment 2

[0036] Example 2: Preparation of Meropenem Trihydrate

[0037] 40.0 L of deionized water, 21.0 Kg (1.43 mol) of meropenem intermediate, 0.50 L (4.32 mol) of 2,6-lutidine, and 0.3 Kg of 10% palladium on carbon were sequentially added into a 100 L hydrogenation reactor. Nitrogen was replaced several times, hydrogen was replaced several times, and finally hydrogen was passed to the pressure of 1.5 MPa in the kettle, the temperature was controlled at 20°C, and stirred for 2 hours. Stirring was stopped, hydrogen was discharged and replaced with nitrogen. Filter and recover the filter cake for reuse; add 160L of acetone to the filtrate, stir and crystallize at 10°C for 4h. Filtration and vacuum drying yielded 0.436 Kg of off-white solid with a molar yield of 69.5%, an HPLC purity of 99.2%, and a heavy metal content of <10 ppm.

Embodiment 3

[0038] Example 3: Preparation of Meropenem Trihydrate

[0039] 40.0 L of deionized water, 21.0 Kg (1.43 mol) of meropenem intermediate, 0.65 L (5.61 mol) of 3,5-lutidine, and 0.1 Kg of 10% palladium on carbon were sequentially added into a 100 L hydrogenation reactor. Nitrogen was replaced several times, hydrogen was replaced several times, and finally hydrogen was passed to the pressure of 2MPa in the kettle, the temperature was controlled at 10°C, and stirred for 2h. Stirring was stopped, hydrogen was discharged and replaced with nitrogen. Filter and recover the filter cake for reuse; add 160L of acetone to the filtrate, stir and crystallize at 0°C for 4h. After filtration and vacuum drying, 0.459 Kg of off-white solid was obtained, the molar yield was 73.2%, the HPLC purity was 99.0%, and the heavy metal content was <10 ppm.

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 preparation method of meropenem as shown in the formula 1 and its hydrate. According to the method, a meropenem intermediate I is used as a raw material and a single solvent water is used as a reaction solvent to perform a hydrogenated deprotection reaction in the presence of alkali and a catalyst. The single solvent water is used as a reaction solvent in the method provided by the invention, thus solving the problem of dissolving the catalyst by the reaction solvent, reducing product degradation and raising product purity. In addition, the preparation method is economical, safe and environmentally friendly, and is more suitable for industrial operation at large scale.

Description

technical field [0001] The invention belongs to the field of synthesis of carbapenem antibiotics, in particular to an improved preparation method of carbapenem compound meropenem. Background technique [0002] Meropenem, also known as Meropenem, Meropenem, the chemical name is 3-[[5-[(dimethylamino)carbonyl]-3-pyrrolidinyl]thio]-6-(1-hydroxyethyl)- 4-methyl-7-oxo-1-azabicyclo[3,2,0]hept-2-ene-2-carboxylic acid, the structural formula is shown in formula 1: [0003] [0004] Meropenem is a second-generation carbapenem antibiotic first developed by Sumitomo Pharmaceuticals Co., Ltd. It was launched in the form of Meropenem trihydrate in January 1995 under the trade name Merrem (美平). . It is the first carbapenem antibiotic that can be used alone, and it is also the first β-methyl carbapenem antibiotic. Because meropenem introduces a methyl group at the C-1 position of the structure, this methyl group is resistant to renal dehydropeptidase-1 (DHP-1), so it does not need to...

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): C07D477/20C07D477/06
CPCY02P20/55
Inventor 张宏武龚登凰吕健马玉秀吴文芳
Owner CSPC ZHONGQI PHARM TECH (SHIJIAZHUANG) CO LTD
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
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