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

Method for preparing cefprozil dimethyl formamide solvate

A technology of propylene dimethyl formamide and solvate, which is applied in the field of preparation of important intermediates of antibiotics, and can solve the problems of high price and unstable silylating reagents, etc.

Active Publication Date: 2014-09-17
CSPC MEGALITH BIOPHARMACEUTICAL CO LTD
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] The object of the present invention is to provide a kind of preparation method of improved cefprozil DMF solvate, this method overcomes the instability of silylating reagent in the existing cefprozil DMF solvate preparation method, expensive, the problems such as product yield is on the low side, The production cost is saved, which is more conducive to the industrial production of cefprozil

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 preparing cefprozil dimethyl formamide solvate
  • Method for preparing cefprozil dimethyl formamide solvate
  • Method for preparing cefprozil dimethyl formamide solvate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Embodiment 1: the preparation of cefprozil DMF solvate (I)

[0042] (1) Synthesis of 7-APCA-tetramethylguanidine salt (compound VII)

[0043] 7-APCA (31.155 g, 0.1298 mol) was suspended in dichloromethane (240 mL), and cooled to -15~-5°C. Tetramethylguanidine (14.928 g, 0.1298 mol) was added dropwise, and the mixture was kept warm and stirred for 30 minutes, and kept warm for later use.

[0044] (2) Synthesis of mixed anhydride (compound VIII)

[0045] Add D-p-hydroxyphenylglycine potassium salt (45.36 g, 0.1497 mol) into a mixed solution of dichloromethane (60 mL), DMF (120 mL) and pyridine (0.39 mL), and stir at room temperature to obtain a suspension. When the temperature was lowered to -35°C, a mixed solution of pivaloyl chloride (18.63 mL) and dichloromethane (60 mL) was added dropwise. After the dropwise addition, continue to stir at the same temperature for 3h.

[0046] (3) Condensation reaction

[0047] Add the 7-APCA-tetramethylguanidine salt prepared in s...

Embodiment 2

[0050] Embodiment 2: the preparation of cefprozil DMF solvate (I)

[0051] (1) Synthesis of 7-APCA-tetramethylguanidine salt (compound VII)

[0052] 7-APCA(III) (31.155 g, 0.1298 mol) was suspended in dichloromethane (240 mL), and cooled to -15~-5°C. Tetramethylguanidine (14.928 g, 0.1298 mol) was added dropwise, and the mixture was kept warm and stirred for 30 minutes, and kept warm for later use.

[0053] (2) Synthesis of mixed anhydride (compound VIII)

[0054] Add D-p-hydroxyphenylglycine potassium salt (45.36g, 0.1497mol) into a mixed solution of dichloromethane (117mL), DMF (74.55mL) and pyridine (0.39mL), and stir at room temperature to obtain a suspension. When the temperature was lowered to -35°C, 18.63 mL of pivaloyl chloride was added dropwise. After the dropwise addition, continue to stir at the same temperature for 2 h, and finally add 62 mL of cold DMF to dilute.

[0055] (3) Condensation reaction

[0056] Add the 7-APCA-tetramethylguanidine salt prepared in s...

Embodiment 3

[0059] Embodiment 3: the preparation of cefprozil DMF solvate (I)

[0060] (1) Synthesis of 7-APCA-tetramethylguanidine salt (compound VII)

[0061] 7-APCA(III) (31.155 g, 0.1298 mol) was suspended in dichloromethane (240 mL), and cooled to -15~-5°C. Tetramethylguanidine (14.928 g, 0.1298 mol) was added dropwise, and the mixture was kept warm and stirred for 30 minutes, and kept warm for later use.

[0062] (2) Synthesis of mixed anhydride (compound VIII)

[0063] Add D-p-hydroxyphenylglycine potassium salt (45.36g, 0.1497mol) into a mixed solution of dichloromethane (117mL), DMF (74.55mL) and pyridine (0.39mL), and stir at room temperature to obtain a suspension. When the temperature was lowered to -35°C, 18.63 mL of pivaloyl chloride was added dropwise. After the dropwise addition, continue to stir at the same temperature for 2 h, and finally add 62 mL of cold DMF to dilute.

[0064] (3) Condensation reaction

[0065] Add the 7-APCA-tetramethylguanidine salt prepared in...

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 an improved method for preparing cefprozil dimethylformamide solvate, the method is to use 7-APCA-guanidine salt shown in formula IV and mixed anhydride shown in formula VI as raw materials under alkaline conditions Condensation reaction is carried out, the obtained reaction solution is hydrolyzed in the presence of an acid, the liquid is separated, DMF is added to the water phase, and the pH value is adjusted with alkali to obtain the cefprozil DMF solvate shown in formula I. The method of the invention avoids the use of expensive and unstable silylating reagents, greatly improves the product yield, reduces production costs, and is a more economical and effective preparation process. Wherein, X+, R6 are as defined in claim 1.

Description

technical field [0001] The present invention relates to a kind of preparation method of important intermediate of antibiotics, in particular to a kind of preparation method of cefprozil dimethylformamide solvate (hereinafter referred to as cefprozil DMF solvate) shown in formula I. [0002] Background technique [0003] The chemical name of cefprozil is (6R,7R)-7-[2-amino-2-(4-hydroxyphenyl)acetamido]-3-[(Z)-propenyl]-3-cephem-4- Carboxylic acid, which is a monohydrate for medicinal use (the structural formula is shown in formula II). This substance is a cephalosporin broad-spectrum antibacterial drug developed by Bristol-Myers Squibb Company of the United States. + , G - Bacteria and anaerobic bacteria have strong antibacterial activity, against G + Bacteria are particularly prominent. [0004] [0005] Cefprozil DMF solvate is an important intermediate in the synthesis of cefprozil. [0006] In U.S. Patents US20040087786, US20090048460, Chinese patents CN1694888...

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 Patents(China)
IPC IPC(8): C07D501/22C07D501/04
Inventor 宋灵杰刘长鹰郑旭光付德才康钰
Owner CSPC MEGALITH BIOPHARMACEUTICAL 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