Preparation method of 7-phenylacetamido-3-vinyl-4-p-methoxy benzyl ester cefotaximate

A technology of p-methoxybenzyl ester and phenylacetamide, applied in the direction of organic chemistry, bulk chemical production, etc., can solve the problems of production environment pollution, low yield, long reaction steps, etc., and achieve reduction of production cost and operation process The effect of simplicity and mild reaction conditions

Active Publication Date: 2014-07-16
湖北凌晟药业股份有限公司
View PDF6 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the raw materials of the first preparation route are easy to obtain, the reaction steps are long, the yield is low, and it is difficult to realize industrialization
The second route requires expensive organosilicon reagents such as hexamethylsilyldisilazane and iodotrimethylsilane and strong organic bases. The reaction process needs to be completed under absolutely anhydrous conditions. The production conditions are harsh, difficult to control, and also difficult for the industry. change
The improved method of quaternary ph...

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022]24.5g (0.05mol) of 7-phenylacetamido-3-chloromethyl-4-cephenoic acid p-methoxybenzyl ester, 7.5g (0.05mol) of sodium iodide, 14.4g (0.055mol) of triphenyl Phosphine was added to 75mL of dichloromethane, 75mL of acetone, and 75mL of water mixture in sequence, and stirred evenly; 45g of 35-40% formaldehyde solution was added. 5% sodium hydroxide solution was added dropwise at room temperature to control the pH to 7-9, and the reaction progress was monitored by HPLC. After 10 h, the reaction was basically over. Add 100 mL of dichloromethane, and stir to dissolve the resulting solid. The layers were separated, and the upper layer was reserved for application; the lower layer was washed with 10% sodium chloride solution, concentrated, and dichloromethane and acetone were recovered. Add 300mL of methanol to the residue, stir to disperse, concentrate under reduced pressure until the mass of methanol is 120-130g, stir at room temperature, slowly add 60g of water dropwise, cont...

Embodiment 2

[0024] Add 10mL35-40% formaldehyde solution and 0.5g hydrosulfite to the aqueous phase obtained in Example 1, then add 75mL dichloromethane and 75mL acetone, and stir to obtain a mixed solution; at room temperature, add 24.5g (0.05mol) 7- Phenylacetamido-3-chloromethyl-4-cephemic acid p-methoxybenzyl ester, 14.4 g (0.055 mol) of triphenylphosphine. 5% sodium hydroxide solution was added dropwise at room temperature to control the pH to 7-9, and the reaction progress was monitored by HPLC. After 10 h, the reaction was basically over. Post-treatment was carried out according to the method of Example 1 to obtain 18.5 g of a white solid with a yield of 79.7% and a purity of 98.2% (HPLC).

Embodiment 3

[0026] According to the feeding ratio and operation method of Examples 1 and 2, the water phase application process is investigated respectively. Add a small amount of hydrosulfite and active carbon to decolorize and filter the aqueous phase obtained each time, and apply mechanically 5 times. The experimental results are shown in the table below:

[0027] frequency GCLE / g Product / g Yield (%) purity(%) 1 24.5 18.5 79.7 97.3 2 24.5 18.0 77.6 97.6 3 24.5 19.1 82.3 96.8 4 24.5 18.4 79.3 97.2 5 24.5 19.0 81.9 96.0

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 discloses a preparation method of 7-phenylacetamido-3-vinyl-4-p-methoxy benzyl ester cefotaximate and belongs to the Chemical medicine field. The preparation method comprises the following steps: carrying out quaternary phosphorization and vinyl reaction at the same time on 7-phenylacetamido-3-chloromethyl-4-p-methoxy benzyl ester cefotaximate (GCLE), sodium iodide, triphenylphosphine and formaldehyde solution in a mixed system of dichloromethane, acetone and water to obtain 7-phenylacetamido-3-vinyl-4-p-methoxy benzyl ester cefotaximate; and removing 7-amino and 4-carboxyl protecting group according to known methods to prepare cefixime and cefdinir nuclear parent 7-AVCA (7-amino-3-vinyl-4-cephalosporanic acid). The aqueous phase comprising sodium iodide and excessive formaldehyde can be repeatedly applied, so that the utilization ratio of sodium iodide is remarkably improved, the production cost is lowered, and the environmental pollution caused by formaldehyde is reduced. The preparation method disclosed by the invention is low in production cost, simple in operating method and suitable for industrialized production and the raw materials are easily available in the preparation process.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate 7-phenylacetamido-3-vinyl-4-cephem acid p-methoxybenzyl ester, which belongs to the field of medicine and chemical industry. Background technique [0002] 7-Amino-3-vinyl-4-cephemic acid (7-AVCA) is the mother nucleus for the production of cefixime and cefdinir. The preparation methods reported in the literature include: 1. Using penicillin G potassium salt as a starting material, it is prepared through a series of reactions such as ring opening and ring expansion; ), treated with organic silicon reagents, and prepared by reacting with formaldehyde under strong alkali and anhydrous conditions; As a raw material, it can be prepared by removing 4-carboxyl and 7-amino protecting groups through quaternary phosphine and vinylation. Although the raw materials of the first preparation route are easy to obtain, the reaction steps are long and the yield is low, so it is difficult t...

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): C07D501/04C07D501/22
CPCY02P20/55C07D501/04C07D501/22
Inventor 付德才吕海军郑美玲赵爽赵光耀
Owner 湖北凌晟药业股份有限公司
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