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

Preparation technology of flomoxef sodium

The invention relates to a technology for sodium fluorooxycephate and a preparation process, which is applied in the field of organic synthesis, and can solve the problems of residual organic acid, unclear amount of sodium bicarbonate, and difficulty in removing inorganic impurities, so as to achieve simple operation, avoid the problem of residual inorganic salt, and stabilize the process. Effect

Active Publication Date: 2019-08-20
ZHEJIANG YONGNING PHARMA
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In order to solve the above-mentioned problems such as the unclear dosage of sodium bicarbonate in the freeze-drying process of fluoxetal sodium, the difficulty of removing inorganic impurities and the residual organic acid in the solvent crystallization process, the present invention provides a new preparation process, which is easy to operate and easy to form. Sufficient, can effectively remove inorganic and organic impurities, and there is no organic acid residue, the final product has high purity and high content, suitable for industrial production

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 technology of flomoxef sodium
  • Preparation technology of flomoxef sodium
  • Preparation technology of flomoxef sodium

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0028] In the following examples, the preparation method of fluoxetal acid refers to patent documents CN105801601A and CN105037393A, and the specific operation steps are as follows: the fluoxetal intermediate ((6R,7R)-7-(2-((difluoromethyl) Thio)acetylamino)-3-(((1-(2-hydroxyethyl)-1H-tetrazol-5-yl)thio)methyl)-7-methoxy-8-oxo-5-oxo Hetero-1-azabicyclo[4.2.0]oct-2-ene-2-(benzhydryl)carboxylate) was added to m-cresol, heated to 65-70°C and stirred for 2.5 hours, the reaction ended After cooling to 0-5°C, add 5% sodium bicarbonate solution to adjust the pH to 8.0, wash the aqueous layer three times with ethyl acetate, adjust the pH to 3.0 with 5% hydrochloric acid, extract with ethyl acetate, and wash with anhydrous sulfuric acid Sodium drying, filtration, and concentration under reduced pressure can give fluoxetal acid as a foaming solid. The purity measured by HPLC was 99.21%, and the impurity 1-(2-hydroxyethyl)-5-mercapto-1H-tetrazolium was 0.34%.

[0029] Wherein, in the e...

Embodiment 1

[0032] Add 49.6g (0.1mol) of fluoxetal acid in the beaker, add 250ml of acetone with a water content of 3%, stir to dissolve, cool to 0-5°C, add 9.2g (0.11mol) of sodium bicarbonate solid, and stir for 0.5 hours Add 50g of anhydrous sodium sulfate, stir for 0.5 hours, filter, cool the filtrate to 0-5°C, add 250ml of ethyl acetate dropwise to the filtrate, continue stirring at the same temperature for 3 hours, filter, and filter the cake with a small amount of Rinse with ethyl acetate, and then vacuum dry at 30-35°C for 6 hours to obtain 47.6g of white solid powder with a yield of 91.8% and a purity of 99.60%. The impurity 1-(2-hydroxyethyl)-5-mercapto-1H- Tetrazolium content is 0.11%, all the other impurities are less than 0.1% (see attached figure 1 ), the measured moisture content is 0.82%, the pH value is 5.05, the optical rotation is -10.0°, and the solvent residue: acetone 0.12%, ethyl acetate 0.07%.

[0033] Referring to the operation of Example 1, the type of organic s...

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 technology of flomoxef sodium. The preparation technology comprises the following steps: flomoxef ((6R, 7R)-7-(2-((difluoromethyl)thio)acetylamino)-3-(((1-(2-hydroxyethyl)-1H-tetrazole-5-yl)thio)methyl)-7-methoxy-8-oxo-5-oxa-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid) used as a raw material is reacted with an inorganic sodium salt in a water-containing organic solvent A to obtain an aqueous flomoxef sodium solution, the aqueous flomoxef sodium solution is dehydrated with anhydrous sodium sulfate, an organic solvent B is dropwise added, and the obtained solution is crystallized to obtain solid flomoxef sodium. The preparation technology avoids the problem of organic acid residue in traditional solvent crystallization technologies, avoids the problems of unclear use amount of sodium bicarbonate and the residual of the inorganic salt in the lyophilization process, and has wide application values.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation process of fluoxyceph sodium. Background technique [0002] Fluoxetal sodium is a broad-spectrum antibiotic of the oxacephalosporin class developed by Shionogi Pharmaceutical Co., Ltd. in Japan in 1988. Its antibacterial spectrum is similar to other third-generation cephalosporins, and it has good activity against Gram-negative positive bacteria and anaerobic bacteria, especially against methicillin-resistant Staphylococcus aureus (MRSA). It is highly stable to β-lactamase, hardly produces drug resistance, and has very low nephrotoxicity. [0003] The preparation methods of fluoxyceph sodium reported so far include freeze-drying and solvent crystallization. [0004] Patent literature CN103524534A discloses a method for preparing fluoxyceph sodium through a freeze-drying process, in which sodium bicarbonate solution is added dropwise to fluoxy...

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): C07D505/20C07D505/08
CPCC07D505/08C07D505/20
Inventor 叶天健陈鑫叶继华叶福康郑豪金彬书
Owner ZHEJIANG YONGNING PHARMA