Preparation method of high-purity Levofloxacin semihydrate

A levofloxacin and hemihydrate technology, which is applied in the field of drug synthesis, can solve the problems of low purity of levofloxacin hemihydrate finished products, difficult microbial degradation, and many solvent residues, and achieve the effects of good quality and appearance, high purity, and low cost

Inactive Publication Date: 2010-10-20
浙江东亚药业股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Adopt above-mentioned method to prepare levofloxacin hemihydrate, the boiling point of the organic solvent used is higher, energy consumption is big during reclaiming, is difficult to reclaim; Adopt halogenated hydrocarbon, DMSO and DMF and other organic solvents, discharge into waste water and microorganism is difficult to degrade, to the microorganism The growth will be inhibited or even poisoned; the levofloxacin crude product is obtained by extracting levofloxacin from water with halogenated hydrocarbons, and there are many solvent residues, and the final product of levofloxacin hemihydrate has a low purity

Method used

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  • Preparation method of high-purity Levofloxacin semihydrate
  • Preparation method of high-purity Levofloxacin semihydrate

Examples

Experimental program
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Effect test

Embodiment 1

[0033] Put 100 grams of raw material levoxyfluorocarboxylic acid into a 1000ml four-necked flask, then add N-methylpiperazine, solvent DMSO and triethylamine to react with piperazine at 85℃ for 6 hours, and recover the solvent DMSO under reduced pressure And triethylamine and N-methylpiperazine; after concentrating to dryness, add 400 grams of pure water, increase the temperature to 75°C until the solids are completely dissolved, add ammonia water dropwise at this temperature until the pH of the solution is 7.0, and cool to After keeping the temperature at 30~35°C for half an hour, filter and rinse the filter cake with a little pure water to obtain crude levofloxacin I.

[0034] Add the crude levofloxacin I obtained above and 700ml of ethanol into a 1000ml four-necked flask, raise the temperature to 70°C until the solids are completely dissolved, add hydrochloric acid dropwise to pH 3.0, raise the temperature to reflux for half an hour, lower the temperature to 30°C, and filter to...

Embodiment 2

[0038] Put 100 grams of levoxyfluorocarboxylic acid as raw material into a 1000ml four-necked flask, then add N-methylpiperazine and solvent DMF to react with piperidine at 90℃ for 6 hours, and recover solvent DMF and N-methyl under reduced pressure. Piperazine; after concentrating to dryness, add 300 grams of pure water, increase the temperature to 80°C until the solid is completely dissolved, add ammonia water dropwise at this temperature, until the pH of the solution is 7.0, reduce the temperature to 30-35°C, and keep it warm for half an hour After filtering, the filter cake is rinsed with a little pure water to obtain crude levofloxacin I.

[0039] Add the crude levofloxacin I obtained above and 600ml of ethanol into a 1000ml four-necked flask, raise the temperature to 75°C until the solids are completely dissolved, add hydrochloric acid dropwise to pH 3.0, raise the temperature to reflux for half an hour, cool to 20°C, and filter to obtain levofloxacin salt Acid salt.

[0040...

Embodiment 3

[0043] Put 100 grams of raw material levoxyfluorocarboxylic acid into a 1000ml four-necked flask, then add N-methylpiperazine, solvent DMSO, and react with piperazine at 95℃ for 6 hours, and recover the solvent DMSO and N-methyl under reduced pressure. Piperazine; After concentrating to dryness, add 500 grams of pure water, increase the temperature to 70°C until the solid is completely dissolved, add ammonia water dropwise at this temperature, until the pH of the solution is 7.0, reduce the temperature to 20-30°C, and keep it warm for half an hour After filtering, the filter cake is rinsed with a little pure water to obtain crude levofloxacin I.

[0044] Add the crude levofloxacin I obtained above and 800ml of ethanol into a 1000ml four-necked flask, raise the temperature to 78°C until the solids are completely dissolved, add hydrochloric acid dropwise to pH 2.0, heat and reflux for half an hour, cool to 10°C, and filter to obtain levofloxacin salt Acid salt.

[0045] Add 3 times ...

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Abstract

The invention provides a preparation method of high-purity Levofloxacin semihydrate, which belongs to the technical field of the medicine synthesis, and solves the problems of the present preparation method that the prepared Levofloxacin semihydrate is difficult to recycle and has low purity and the used organic solvent is difficult to degrade. The preparation method comprises the following steps: a. preparing Levofloxacin salt; b. preparing Levofloxacin crude product II; c. preparing Levofloxacin semihydrate. The Levofloxacin semihydrate prepared by the preparation method has the advantages of high purity, good quality and appearance, high titration content, high recycling rate, low cost and good environmental-protection performance.

Description

Technical field [0001] The invention relates to a method for preparing a fluoroquinolone drug intermediate, in particular to a method for preparing a high-purity levofloxacin hemihydrate, and belongs to the technical field of drug synthesis. Background technique [0002] Fluoroquinolones have achieved great success in clinical anti-infective treatment due to their high-efficiency, broad-spectrum, and low-toxicity antibacterial properties. Ofloxacin and Levofloxacin developed by Japan's Daiichi Pharmaceutical Company are among them. The excellent variety. Levofloxacin is the S enantiomer of racemic ofloxacin, and the antibacterial activity of ofloxacin is mainly attributed to the S enantiomer. [0003] Levofloxacin is a chiral fluoroquinolone drug, its chemical name is S-(-)-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxy-2 ,3-Dihydro-7H-pyridine-[1,2,3,-de][1,4]benzoxazine-6-carboxylic acid (CAS Registry Number: 100986-85-4). The chemical structural formula of levofloxacin i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/06
Inventor 何小鹏李日生高威龙刘建森池正明
Owner 浙江东亚药业股份有限公司
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