Preparation method for Azlocillin sodium

Abstract

The invention relates to a preparation method for Azlocillin sodium, which belongs to the synthetic technical field of antibiotics. The preparation method comprises the following steps: preparing a solution used for a condensation reaction, drawing dichloromethane into a reactor, putting ampicillin into the reactor with stirring, controlling the weight ratio of dichloromethane to ampicillin, thencooling and controlling the reduced temperature, then regulating the pH value to alkalescence by a pH regulator to obtain an solution used for condensation reaction; performing a condensation reaction; extracting and separating; crystallizing; drying; performing a salifying reaction; decoloring; freezing and drying; crushing. The invention has the advantages that the preparation method is capableof simplifying the operation, reducing the usage of the chemical solutions and the risks on environmental pollution; and has simple operation; can effectively avoid the loss caused by chromatography,raise the yield of Azlocillin sodium; and has mild salifying reaction condition, reduce the risk that Azlocillin sodium can be decomposed in alkali. The content of a single impurity of the obtained Azlocillin sodium dried product is lower than 0.6 percent and the content of total impurity of the obtained Azlocillin sodium dried product is lower than 1 percent which are obviously superior to the pharmacopoeia standard.

Description

technical field [0001] The invention belongs to the technical field of synthesis of antibiotic drugs, and in particular relates to a preparation method of azlocillin sodium. Background technique [0002] Azlocillin sodium (English name: Azlocillin Sodium), its chemical name is: (2S, 5R, 6R)-3,3-dimethyl-6-[(R)-2-(2-oxo-1 -imidazolidinecarboxamido)-2-phenylacetamido]-7-oxo-4-thia-1-azabicyclo[3,2,0]heptane-2-carboxylic acid sodium salt. [0003] [0004] Molecular formula: C 20 h 22 N 5 NaO 6 S [0005] Molecular weight: 483.47 [0006] Azlocillin sodium was first developed by Bayer Company of Germany, and it went on the market in May 1977. Since the 1980s, it has been used in the United States, Britain and other countries. In 1983, it was included in the supplementary volume of the 20th edition of the US Pharmacopoeia. It is still recorded that its bactericidal effect on Pseudomonas aeruginosa is about ten times greater than that of carbenicillin, and it also has t...

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Problems solved by technology

[0008] Typical bibliographical reports are such as: "A kind of preparation method of azlocillin sodium" recommended by the invention patent authorization announcement number CN1305874C. Because the method adopts a solvent crystallization process, it needs to cooperate with ethyl acetate and ethanol as a solvent for crystallization operation, so that Troublesome operation, large amount of chemical solvent used, high cost and risk of damage to the environment

Another example: "A high-purity azlocillin sodium and its powder injection production method" provided by CN101265265B. Although this method has the advantages mentioned in the instructions, it is not only cumbersome to operate due to the need to use a chromatographic column, but also chromatographic Operation will cause loss and affect product yield

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