Method for preparing 3-descarbamoyl-cefuroxime acid

Abstract

The invention relates to a method for preparing 3-descarbamoyl-cefuroxime acid. The method comprises the following steps of: (1) dissolving 7-aminocephalosporanic acid (7-ACA) in water or a methanol solution to prepare a 7-ACA solution, and performing hydrolysis reaction to obtain a 3-deacetyl-7-aminocephalosporanic acid (7-DACA) solution; (2) dissolving an acylchlorination reagent in a solvent, adding a cosolvent, adding (Z)-2-methoxyimino-2-(furyl-2-yl)acetic acid ammonium salt (SIMA), reacting, filtering, adding water or performing rotary evaporation to remove the excessive acylchlorination reagent, performing vacuum rotary evaporation, adding a homogenization reagent, and dissolving to obtain a (Z)-2-(furyl-2-yl)-2-(methoxyimino)-acetyl chloride (SMIF-Cl) solution; (3) adding the homogenization reagent into the 7-DACA solution, dripping the SMIF-Cl solution, regulating the pH value, preserving heat and reacting to obtain a reaction solution; and (4) decolorizing the reaction solution, regulating the pH value, adding purified water, growing a crystal, filtering, and performing vacuum drying. Reactants form a homogeneous system by adding the homogenization reagent, so that the contact area of the reactants is expanded, the reaction rate is increased, and reaction time is shortened.

Description

technical field [0001] The invention relates to a preparation method of cephalosporin antibiotic intermediate 3-decarbamoyl-cefuroxin acid, belonging to the technical field of drug synthesis. technical background [0002] Cefuroxime, the compound (6R,7R)-3-carbamoyloxy-7-[(Z)-2-(furan-2-yl)-2-methoxyaminoacetamido]- 3-Cephem-4-carboxylic acid, since it was developed and listed by the British Glaxo company in 1957, has been clinically used due to its good and balanced antibacterial activity, broad-spectrum antibacterial activity and stability to β-lactamase. been widely applied. my country began to research and develop cephalosporins in the 1960s, and has successfully developed dozens of varieties. But in recent years, only about 10 varieties have been actually produced, among which only cefuroxime is a second-generation cephalosporin. Since the good and balanced antibacterial activity of the second-generation cephalosporins cannot be replaced by the first and third genera...

AI Technical Summary

Problems solved by technology

[0011] 1. Enzymatic preparation of 7-deacetyl cephalosporanic acid requires a special esterase for hydrolysis, which is expensive and not suitable for large-scale production; and the enzymatic hydrolysis method needs to be reacted at a relatively high temperature for a long time, which is not conducive to 7-ACA and 7-DACA stabilization;

[0012] 2. The crystallization of 7-deacetylcephalosporanic acid prepared after hydrolysis of 7-ACA is relatively fine, which makes it difficult to filter and dry, and it is difficult to realize industrial production; and the acid adjustment process is easy to generate a lactone with properties very similar to 7-DACA , it is difficult to remove in post-processing;

[0013] 3. There are many kinds of solvents used in the synthesis process, and solvent recovery is difficult; crystallization and crystal growth in organic solvents, the residual amount of solvent is relatively large;

[0014] 4. The yield is low;

[0015] 5. The temperature (-40~-50℃) is low, and the requirements for refrigeration equipment and heat preservation measures are strict; the cycle is long and the energy consumption is large

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