Unlock instant, AI-driven research and patent intelligence for your innovation.

Cefprozil preparation method

A technology of cefprozil and cephalosporin, which is applied in the field of pharmaceutical and chemical technology synthesis, and can solve problems such as non-compliance

Active Publication Date: 2021-04-23
苏州盛达药业有限公司 +1
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most of the domestic chemical synthesis methods are based on the second route, with a yield of about 80%, and the quality conforms to the Chinese Pharmacopoeia, but does not conform to the EU and US Pharmacopoeia

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
  • Cefprozil preparation method
  • Cefprozil preparation method
  • Cefprozil preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] 1000ml dry reaction flask, add APCA 100g (0.4168mol), 430ml dichloromethane, add HMDS 56g (0.3468mol), add dropwise TMC 37.7g (0.3468mol), rinse with 10ml dichloromethane, heat up to 42-44°C with reflux , time reflux for 6 hours, cool down to -25~-30°C; add 138.8g (0.4576mol) of HPDS and 420ml of dichloromethane to a 2000ml dry reaction bottle, cool down to -60~-70°C with liquid nitrogen, add 300ml of DMF, add CBE 49g (0.4516mol), rinsed with 20ml of dichloromethane, and reacted at -40±2°C for 2 hours, resulting in a colorless clear liquid. After completion, cool down to -75~-80°C. Transfer the reflux liquid to the mixed anhydride, transfer over 10 minutes, rinse with 20ml of dichloromethane, control the temperature at -60~-70°C, react for 2-3 hours, and measure APCA residue 0.48 by HPLC mg / ml. After the acylation is qualified, add a mixed solution of 250ml of purified water + 55ml of concentrated hydrochloric acid, stir for 30min, let stand to separate layers, slowly ...

Embodiment 2

[0056] 1000ml dry reaction flask, add APCA 100g (0.4168mol), 430ml dichloromethane, add HMDS 56g (0.3468mol), add dropwise TMC 37.7g (0.3468mol), rinse with 10ml dichloromethane, heat up to 42-44°C with reflux , timed reflux for 5 hours, cooled to -25~-30°C; 2000ml dry reaction bottle, added 140g (0.462mol) of HPDS, 420ml of dichloromethane, cooled to -60~-70°C with liquid nitrogen, added 300ml of DMF, added 50g of CBE (0.4608mol), rinsed with 20ml of dichloromethane, and reacted at -40±2°C for 2 hours, resulting in a colorless clear liquid. After finishing, cool down to -75~-80°C. Transfer the reflux liquid to the mixed anhydride, turn over in 10 minutes, rinse with 20ml of dichloromethane, control the temperature at -65~-70°C, react for 2-3 hours, and measure APCA residue 0.56 by HPLC mg / ml. After the acylation is qualified, add a mixed solution of 250ml of purified water + 55ml of concentrated hydrochloric acid, stir for 30min, let stand to separate layers, slowly add 1000...

Embodiment 3

[0061] 1000ml dry reaction flask, add APCA 100g (0.4168mol), 430ml dichloromethane, add HMDS 56g (0.3468mol), add dropwise TMC 37.7g (0.3468mol), rinse with 10ml dichloromethane, heat up to 42-44°C with reflux , time reflux for 4 hours, cool down to -25~-30°C; add 145g (0.4785mol) of HPDS (0.4785mol) and 420ml of dichloromethane to a 2000ml dry reaction bottle, cool down to -60~-70°C with liquid nitrogen, add 300ml of DMF, add CBE 51.8 g (0.4774mol), rinsed with 20ml of dichloromethane, and reacted at -40±2°C for 2 hours, resulting in a colorless clear liquid. After finishing, cool down to -75~-80°C. Transfer the reflux liquid to the mixed anhydride, turn it over in 10 minutes, rinse with 20ml of dichloromethane, control the temperature at -60~-65°C, react for 2-3 hours, and measure APCA residue 0.73 by HPLC mg / ml. After the acylation is qualified, add a mixed solution of 250ml of purified water + 55ml of concentrated hydrochloric acid, stir for 30min, let stand to separate l...

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 cefprozil preparation method, which comprises the steps of carrying out a silanization reaction on APCA, TMC and HMDS, forming a mixed anhydride solution from HPDS, DMF and CBE, carrying out an acylation reaction on the reaction liquid after the silanization reaction and the mixed anhydride solution, and after the reaction is ended, carrying out acidification hydrolysis, layering, adding DMF to the aqueous phase, and crystallizing to obtain a cefprozil DMF compound, then adding the cefprozil DMF compound into water for conversion reaction, and crystallizing to obtain cefprozil. The feeding molar weight of the HPDS is 1.05-1.20 times of the feeding molar weight of the APCA, and the feeding molar weight of the CBE is 0.95-1.02 times of the feeding molar weight of the HPDS. The preparation method provided by the invention is high in yield and can reduce the generation of impurity (Z)-cefprozil ethoxyformate, so that the cefprozil product meets the European Union pharmacopoeia standard.

Description

technical field [0001] The invention belongs to the technical synthesis field of medicine and chemical industry, and in particular relates to a preparation method of cefprozil. Background technique [0002] Cefprozil (Cefprozil hydrate) commodity Shifujie or Yidai, its main component and chemical name is (6R,7R)-7-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino] -8-Oxo-3-[(E)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid hydrate, molecular formula: C18H19N3O5SH2O, molecular weight: 407.44, its structural formula is: [0003] [0004] Cefprozil is an oral cephalosporin antibiotic, which was developed by Bristol-Myers Company of the United States and the Tokyo Research Institute, and was approved by the FDA in December 1992. Cefprozil is a second-generation cephalosporin drug with broad-spectrum antibacterial activity. The bactericidal mechanism of the drug is to bind to the penicillin-binding proteins (PBPs) on the bacterial cell membrane, hindering ...

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): C07D501/22C07D501/06C07D501/04
CPCC07D501/22C07D501/06C07D501/04
Inventor 杨虎星韩雪英刘玉良温雄飞
Owner 苏州盛达药业有限公司