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Preparation method of cefuroxime axetil

A technology of cefuroxime axetil and cefuroxime axetil, which is applied in the field of preparation of cefuroxime axetil, can solve the problems of long reaction time, harsh operating conditions, and many impurities in production, and achieve shortened production cycle, mild process conditions, and improved product quality. quality effect

Active Publication Date: 2013-12-11
GUANGDONG LIGUO PHARMACY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] First: Paraldehyde is unstable, easily oxidized into carboxylic acid, and easily decomposed into acetaldehyde under acidic conditions;
[0008] Second: Potassium carbonate is used as the reaction catalyst, which is easy to absorb water and is alkaline, which leads to a decrease in catalytic effect, low product conversion rate, long reaction time, many impurities in production, and dark color;
[0009] Third: Use isopropanol and n-hexane to crystallize. The two solvents have azeotropic phenomenon and are not easy to separate, which brings difficulties to industrial production and recovery.
Although the method shortens the production cycle, potassium carbonate is used as the catalyst, the product conversion rate is low, the impurities are many, the color is deep, the operating conditions are harsh, the energy consumption is large, and the production is not easy to control

Method used

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  • Preparation method of cefuroxime axetil

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Add 150 mL of dimethylformamide to the reaction flask, add 15 g of cefuroxime acid under stirring, stir and dissolve until clear, cool the solution to 0°C; slowly add 15 mL of 1-bromoethyl acetate dropwise; when 1-bromoethyl After the diethyl acetate was added dropwise, 1.5g of copper chloride catalyst was added, and the temperature of the solution was raised to 15°C to continue the stirring reaction for 0.5 hours. The reaction process was monitored by HPLC, and the reaction residue of cefuroxime acid was controlled to be ≤1.0%;

[0041] After the reaction is complete, add 120ml of ethyl acetate under stirring and stir for 15 minutes. After completion, add 10% sodium chloride solution and stir for extraction for 20 minutes. Leave to stand and separate, remove the lower aqueous phase to obtain the upper organic phase and transfer it to the reaction bottle Add 90mL of 3% hydrochloric acid aqueous solution to the organic phase again, stir and wash for 20 minutes, let stand ...

Embodiment 2

[0044] Add 150 mL of dimethylformamide to the reaction flask, add 16.5 g of cefuroxime acid under stirring, stir and dissolve until clear, cool the solution to 2°C; slowly add 15 mL of 1-bromoethyl acetate; when 1-bromo After the ethyl acetate was added dropwise, 1.7 g of copper chloride catalyst was added, and the temperature of the solution was raised to 20° C. to continue stirring and reacting for 1.0 hour. The reaction process was monitored by HPLC, and the reaction residue of cefuroxime acid was controlled to be ≤1.0%;

[0045] After the reaction is complete, add 148.5ml of ethyl acetate under stirring and stir for 15 minutes. After completion, add 10% sodium chloride solution, stir and extract for 20 minutes, let stand for stratification, and remove the lower aqueous phase to obtain the upper organic phase and transfer it to the reaction bottle Add 99 mL of 3% hydrochloric acid aqueous solution to the organic phase again, stir and wash for 20 minutes, let stand to separat...

Embodiment 3

[0048] Add 150 mL of dimethylformamide to the reaction flask, add 18 g of cefuroxime acid under stirring, stir and dissolve until clear, cool the solution to 5°C; slowly add 21.6 mL of 1-bromoethyl acetate; when 1-bromoethyl acetate After the ethyl acetate was added dropwise, 2.3 g of copper chloride catalyst was added, and the temperature of the solution was raised to 25° C. to continue stirring and reacting for 1.0 hour. The reaction process was monitored by HPLC, and the reaction residue of cefuroxime acid was controlled to be ≤ 1.0%;

[0049] After the reaction is complete, add 180ml of ethyl acetate under stirring and stir for 15 minutes. After completion, add 10% sodium chloride solution and stir for extraction for 20 minutes. Let stand to separate layers, remove the lower phase water phase to obtain the upper phase organic phase and transfer it to the reaction bottle Add 135mL3% hydrochloric acid aqueous solution to the organic phase again, stir and wash for 20 minutes, ...

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Abstract

The invention discloses a preparation method of cefuroxime axetil. The method comprises the following steps: completely dissolving cefuroxime acid in dimethylformamide, and carrying out esterification reaction with 1-bromethylacetate under the catalytic action of cupric chloride; and hydrolyzing with ethyl acetate and sodium chloride solution, extracting, carrying out vacuum distillation, crystallizing with cyclohexane, carrying out vacuum filtration, and drying to obtain high-purity cefuroxime axetil. The cupric chloride, which has the advantages of no toxicity, no harm and high catalytic efficiency, is preferably used as the catalyst; the cyclohexane for crystallization is easy to recover and reutilize, thereby lowering the production cost; and meanwhile, the method has the advantages of mild and controllable reaction conditions, short production cycle and lower energy consumption, and is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of pharmaceutical manufacturing, in particular to a preparation method of cefuroxime axetil. Background technique [0002] Cefuroxime axetil, chemical name: (6R,7R)-7-[2-furyl(methoxyimino)acetamido]-3-carbamoyloxymethyl-8-oxo-5-thia- 1-Azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; generic drug name Cefuroxime Axetil; also known as cefuroxime axetil; molecular formula: C 20 h 22 N 4 o 10 S, molecular weight: 510.48, CA registration number: 64544-07-61, its molecular structure is as follows: [0003] [0004] Cefuroxime axetil (Ceftin) was created by GlaxoSmithKline and first launched in the United States in 1988, and its patent expired in 1996. Cefuroxime axetil is a second-generation oral cephalosporin, which has strong fat solubility and good oral absorption. Cefuroxime axetil is an ester of cefuroxime, which releases cefuroxime after hydrolysis in vivo to exert its antibacterial activity. The latter has a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/34C07D501/04
Inventor 许伟龙
Owner GUANGDONG LIGUO PHARMACY
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