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Method for refining high-purity ceftiofur hydrochloride

A technology of ceftiofur hydrochloride and its refining method, which is applied in the direction of organic chemistry, can solve the problems of reducing impurity content, etc., and achieve the effects of uniform particle size distribution, low production cost and simple process

Active Publication Date: 2017-03-08
RINGPU TIANJIN BIOLOGICAL PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this patent preparation process, the prepared ceftiofur free acid mother liquor is directly reacted with hydrochloric acid to generate ceftiofur hydrochloride, and there is no crystallization process of ceftiofur free acid in the middle. Although the process is simplified, it is slightly insufficient in reducing the impurity content.
[0008] The above patents mainly relate to the synthesis process: after the reaction of cefuroxime and AE-active ester, hydrochloric acid is added to prepare ceftiofur hydrochloride, but there are deficiencies in the recrystallization and purification of ceftiofur hydrochloride finished products, in order to solve the problem of ceftiofur hydrochloride Finished products, long-term storage or unqualified solid products, the present invention specifically proposes a recrystallization purification process for ceftiofur hydrochloride

Method used

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  • Method for refining high-purity ceftiofur hydrochloride
  • Method for refining high-purity ceftiofur hydrochloride
  • Method for refining high-purity ceftiofur hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 1. Weigh 100g of ceftiofur hydrochloride raw material, add it to the reaction kettle, then add 250ml of purified water and 250ml of ethanol, stir to dissolve, add 0.5g of powdered activated carbon, stir and decolorize for 20 minutes, filter to obtain ceftiofur hydrochloride solution; Add the filtered ceftiofur hydrochloride solution into the reaction kettle, and adjust the temperature to 20°C. Add 2.5% ammonia water dropwise at a speed of 5ml / min in the reactor to adjust the pH value to 2.8, then add 2500ml of purified water to the reactor, dissolve crystals, separate out solids, filter, and dry to obtain ceftiofur free acid crystals 84.5g.

[0040] 2. Add 170ml of dimethyl sulfoxide to reaction kettle 1, add 84.5g of dry ceftiofur free acid crystals into the reaction kettle, and stir to dissolve. Then concentrated hydrochloric acid was added dropwise to the reaction kettle 1 to adjust the pH value to 0.5, and the reaction was stirred for 30 minutes. Add 1700 mL of pu...

Embodiment 2

[0042] 1. Weigh 100g of ceftiofur hydrochloride raw material, add it to the reaction kettle, then add 340ml of purified water, 660ml of methanol, stir to dissolve, add 1.5g of powdered activated carbon, stir and decolorize for 20 minutes, filter the ceftiofur hydrochloride solution, Obtain ceftiofur hydrochloride solution. Add the filtered ceftiofur hydrochloride solution into the reaction kettle, and adjust the temperature to 50°C. Add 2.5% sodium hydroxide solution dropwise at a speed of 3ml / min in the reactor to adjust the pH value to 2.5, then add 3000ml of purified water to the reactor, dissolve crystals, separate out solids, filter, and dry to obtain ceftiofur Free acid crystals 82.2g.

[0043] 2. Add 250ml of N,N dimethylformamide into Reactor 1, adjust the temperature to 20°C, add 82.2g of dry ceftiofur free acid crystals into Reactor 1, and stir to dissolve. Then concentrated hydrochloric acid was added dropwise to the reaction kettle 1 to adjust the pH value to 1, ...

Embodiment 3

[0045] 1. Weigh 100g of ceftiofur hydrochloride raw material, add it to the reaction kettle, then add 330ml of purified water and 1670ml of ethanol, stir to dissolve, add 3.0g of powdered activated carbon, stir and decolorize for 20 minutes, filter the ceftiofur hydrochloride solution, Obtain ceftiofur hydrochloride solution. Add the filtered ceftiofur hydrochloride solution into the reaction kettle, and adjust the temperature to 45°C. Add pyridine dropwise at a speed of 3ml / min in the reactor, adjust the pH value to 3.3, then add 6000ml of purified water to the reactor, dissolve crystals, separate out solids, filter, and dry to obtain 81.9g of ceftiofur free acid crystals .

[0046] 2. Add 450ml of dimethyl sulfoxide to Reactor 1, adjust the temperature to 35°C, add 81.9g of dry ceftiofur free acid crystals to Reactor 1, and stir to dissolve. Then concentrated hydrochloric acid was added dropwise to the reaction kettle 1 to adjust the pH value to 1.5, and the reaction was s...

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Abstract

The invention provides a method for refining ceftiofur hydrochloride. The method comprises dissolving ceftiofur hydrochloride to be refined in water, an organic solvent or a mixed solution of water and an organic solvent, removing hydrogen chloride molecules in the solution by base or ion exchange resin so that ceftiofur free acid crystals are precipitated from the solution, adding the ceftiofur free acid crystals into the organic solvent, then adding concentrated hydrochloric acid into the solution drop by drop to adjust pH, carrying out a reaction process to obtain ceftiofur hydrochloride, slowly and dropwisely adding the organic solution of ceftiofur hydrochloride into purified water, and carrying out dissolution crystallization to obtain high purity ceftiofur hydrochloride crystals. The method has the advantages of simple process, strong operability and low production cost, and can stably prepare a ceftiofur hydrochloride crystal product with a regular crystal form, uniform particle size distribution and purity greater than 99.7%.

Description

technical field [0001] The invention belongs to the field of chemical synthesis and purification of veterinary raw materials, in particular to a method for recrystallization, purification and purification of high-purity (≥99.7%) ceftiofur hydrochloride. Background technique [0002] Ceftiofur hydrochloride, (6R,7R)-7-[2-(2-aminothiazol-4-yl)(methoxyimino)acetamido]-3-[(2-furylcarbonyl)sulfur Methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. English name: Ceftiofur CAS NO: 103980-44-5, molecular formula: C 19 h 17 N 5 o 7 S 3 .HCL (see figure 1 ). Molecular weight: 560.03. Appearance is off-white to light yellow powder. Insoluble in water, almost insoluble in ethanol, slightly soluble in acetone and tetrahydrofuran, easily soluble in dimethyl sulfoxide and N,N-dimethylformamide. [0003] Ceftiofur is a semi-synthetic third-generation animal-specific cephalosporin. Usually made of sodium salt and hydrochloride for injection. It has a wide antibac...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/12
CPCC07D501/12C07D501/36
Inventor 井丁丁李红艳刘爱玲李旭东夏雪林郑超
Owner RINGPU TIANJIN BIOLOGICAL PHARMA