A kind of environment-friendly preparation method of the intermediate of cefuroxime acid

A technology for cefuroxime acid and intermediates, which is applied in the field of environmental protection preparation of intermediates, can solve problems such as large environmental impact, unsatisfactory yield and quality, and achieves reduction of solvent residues, reduction of the amount of chloride salts and phosphates, Responsive effect

Active Publication Date: 2020-12-08
GUANGDONG LIGUO PHARMACY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide an environmentally friendly preparation method for an intermediate of cefuroxime acid, to solve the problem that the existing process has a greater impact on the environment, and the yield and quality are not ideal.

Method used

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  • A kind of environment-friendly preparation method of the intermediate of cefuroxime acid
  • A kind of environment-friendly preparation method of the intermediate of cefuroxime acid
  • A kind of environment-friendly preparation method of the intermediate of cefuroxime acid

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preparation example Construction

[0024] The present invention relates to a kind of environment-friendly preparation method of the intermediate of cefuroxime acid, comprising:

[0025] A, prepare SMIA acid chloride solution: as figure 1 As shown, dissolve triphosgene in an organic solvent, stir at low temperature, add imidazole at low temperature after fully dissolving, stir at low temperature, and depolymerize triphosgene; figure 2 As shown, add methoxyimidofuran ammonium acetate (SMIA ammonium salt) and continue the low-temperature reaction. After the reaction is completed, add purified water to wash, separate liquid, discard the water phase, and keep the organic phase to obtain methoxyimidefuran B Acid chloride solution (SMIA acid chloride solution); organic solvents include but not limited to esters, alcohols, hydrocarbons, ketones, aldehydes, amines, nitriles, ethers, etc., such as dichloromethane, acetone, ether, methanol, etc. Wait;

[0026] Among them, the CAS registration number of triphosgene: 323...

Embodiment 1

[0045] Dissolve 8g of triphosgene in 70ml of dichloromethane, and control the temperature at -20-0°C under stirring. After fully dissolving, add 0.3g of imidazole, control the temperature at -5°C and add in batches, and the addition will be completed within about 5 minutes. The reaction was stirred for 90-120 minutes. Then add 13 g of SMIA ammonium salt, control the temperature at -20-0° C. and react for about 1-2 hours. HPLC monitoring shows that SMIA is less than 0.5%, and the reaction is basically completed. Add 40ml of cold water to wash twice, separate the liquid, discard the water phase, and keep the organic phase, which is the SMIA acid chloride solution with a purity of 99.2%. In another reaction bottle, add 100ml of pure water, lower the temperature to below 5°C, add 13.5g of D-7-ACA, add dropwise 10% sodium hydroxide solution to dissolve, pay attention to control pH = 7-10, after dissolution, control below Store at 5°C for later use. Add the SMIA acid chloride solu...

Embodiment 2

[0047] Dissolve 2.8g of triphosgene in 70ml of dichloromethane solution, and control the temperature at 0-20°C while stirring. After fully dissolving, add 0.014g of imidazole, control the temperature at -5°C and add in batches, and complete the addition within about 5 minutes. The reaction was stirred for 30-90 minutes. Then add 2.8 g of SMIA ammonium salt, control the temperature at about -20-0° C. and react for about 30-60 minutes. HPLC monitoring shows that SMIA is less than 0.5%, and the reaction is basically completed. Add 40ml of cold water to wash twice, separate the liquid, discard the water phase, and keep the organic phase, which is the SMIA acid chloride solution with a purity of 98.9%. In another reaction bottle, add 1000ml of pure water, lower the temperature to below 5°C, add 1g of D-7-ACA, add 10% sodium hydroxide solution dropwise to dissolve, pay attention to control pH = 7-10, control it below 5 after dissolution ℃ for later use. Add the SMIA acid chloride ...

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Abstract

The invention relates to an environmentally-friendly preparation method of an intermediate of cefuroxime acid. The method comprises the following steps: preparing an SMIA acyl chloride solution by utilizing triphosgene, preparing a D-7-ACA solution, and performing a condensation reaction on the SMIA acyl chloride solution and D-7-ACA solution to obtain DCC. The environmentally-friendly preparationmethod of the intermediate of the cefuroxime acid provided by the invention greatly reduces the amount of a chloride salt and a phosphate salt, and does not use high-boiling-point class-2 solvent dimethylacetamide (DMAC) difficult to recover and soluble in water, thereby greatly reducing environmental pressure, greatly reducing production costs, and steadily improving the product quality; the reaction for preparing the acyl chloride from the triphosgene is thorough, and the prepared acyl chloride has high purity, so that the prepared intermediate DCC also has higher purity; and the high-boiling-point class-2 solvent DMAC is not used; therefore the produced cefuroxime acid has a lower residual solvent, a residual solvent of bulk drug cefuroxime sodium and cefuroxime axetil produced by theintermediate of the cefuroxime acid is greatly reduced, the quality of the final product is better improved, and the yield is increased.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to an environment-friendly preparation method of an intermediate of cefuroxime acid. Background technique [0002] Cefuroxime is a cephalosporin antibiotic developed by the British Glaxo Company and belongs to the second-generation cephalosporin. It inhibits cell division and growth by binding to penicillin-binding proteins (PBPs) on the bacterial cell membrane, and finally lyses and kills the bacteria. Cefuroxime has a broad-spectrum antibacterial effect and a wide range of applications. It can be used for respiratory infections caused by sensitive bacteria, ear, nose, throat infections, urinary tract infections, skin and soft tissue infections, bone and joint infections, gonorrhea, including sepsis and Meningeal and other infections. [0003] Although the current production process of cefuroxime in my country has been close to the level of the original research unit after near...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D501/06C07D501/34
CPCC07D501/06C07D501/34
Inventor 李亮王宝黄泽文曾良兵陈奕开何菁华
Owner GUANGDONG LIGUO PHARMACY
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