CN101172982B - Method of preparing cefpirome sulfate - Google Patents
Method of preparing cefpirome sulfate Download PDFInfo
- Publication number
- CN101172982B CN101172982B CN2006101021195A CN200610102119A CN101172982B CN 101172982 B CN101172982 B CN 101172982B CN 2006101021195 A CN2006101021195 A CN 2006101021195A CN 200610102119 A CN200610102119 A CN 200610102119A CN 101172982 B CN101172982 B CN 101172982B
- Authority
- CN
- China
- Prior art keywords
- cefpirome
- preparation
- exchange resin
- hydriodate
- sulfate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The invention discloses a preparation method of sulfuric acid Cefpirome, and has the steps as follows: Cefpirome hydriodate is changed by the resin through using alkaline negative ion and is processed to get the Cefpirome when using water as solvent, thereby forming salt with full sulfuric acid, ethanol is added to separate out crystal, and then sulfuric acid Cefpirome is obtained. The invention has simple operation, and the obtained product has better quality with higher obtaining rate, moreover, and the solvents with bigger toxicity like toluene are avoided from being used, thereby reducing the three waste pollution.
Description
Technical field
The present invention relates to a kind of preparation method of Cefpirome Sulfate, belong to the synthetic field of medicine.
Technical background
Cefpirome be the 4th generation cynnematin, have broad spectrum antibiotic activity, all effective to staphylococcus, penicillin-fast streptococcus pneumoniae and faecalis.Effect to Pseudomonas aeruginosa is similar to ceftazime, and the pathogenic bacteria of a lot of antibiotics resistants is all had good efficacy, is to the strongest microbiotic of gram positive bacterium anti-microbial activity in the known third generation and the 4th generation cynnematin.The vitriol of cefpirome can be absorbed in stomach well, so cefpirome is made into the form of vitriol usually.Its chemistry is by name: (methoxyl group imido grpup) ethanoyl 1-[[7-[[(2-amino-4-thiazolyl)]-amino]-2-carboxyl-8-oxo-5-thia-1-azabicyclic [4.2.0] oct-2-ene-3-yl] methyl]-6,7-dihydro-5H-cyclopenta pyridine vitriol.Structural formula is as follows:
Preparation method about cefpirome, many reports are arranged both at home and abroad, the method that adopts as GB2098216 is cefotaxime and 2, the 3-pyridine cyclopentene is reaction for a long time under alkaline condition, obtain the cefpirome inner salt through twice column chromatography and twice freeze-drying process then, obtain product with the sulfuric acid salify more at last.This method long reaction time, complex operation, and to equipment requirements also than higher.
Another method is to make the cefpirome hydriodate earlier, and then is converted into vitriol.This is maximum a kind of method of studying at present.A critical step is how the cefpirome hydriodate to be converted into vitriol in this method, and is at present many about the patent and the bibliographical information of this respect.As Korean Patent KR9704047 employing is the method for the iodide ion oxidation in the hydriodate being removed with oxygenants such as sodium iodate, hydrogen peroxide.But this method is difficult to control condition in oxidising process, product is easy to oxidized.Other method is to use ion exchange resin to remove wherein iodide ion, mentioned with solid resin Amberlite IRA 93 or liquid resin Amberlite LA-2 as U.S. Pat 4609653 and to have handled the cefpirome hydriodate, and Chinese patent CN1587267 with cefpirome two iodate hydrogen salts use 711 type strongly basic anion exchange resins remove wherein iodide ion, and with toluene and water as solvent, sulfuric acid acidation, add ethanol again and separate out the crystalline method and prepare Cefpirome Sulfate.The common feature of these methods is to need to use a large amount of noxious solvent toluene in treating processes, make the three wastes handle the comparison difficulty that becomes, and environmental pollution is very big.
Summary of the invention
The objective of the invention is to remove the noxious solvent toluene in the existing solvent system, a kind of preparation method of simple and easy to do Cefpirome Sulfate is provided.
Technical scheme of the present invention is the cefpirome hydriodate to be handled under water as solvent with basic anion exchange resin obtain cefpirome, then with the sulfuric acid salify of sufficient quantity, add ethanol and separate out crystallization, Cefpirome Sulfate.Reaction equation is as follows:
In cefpirome hydriodate quality, the mass volume ratio of cefpirome hydriodate and basic anion exchange resin is 1: 1.5～5.0.
Basic anion exchange resin is selected strongly basic anion exchange resin and weak base anion-exchange resin for use.
Strongly basic anion exchange resin selects that model is 201 * 2,201 * 8,202 * 7 for use, D261, D280, D284, D290, D296, D201GF, 201 * 7, D201, D262.
It is D301R, D301G, D370, D371, D380, D382, D392 that weak base anion-exchange resin is selected model for use.
In cefpirome hydriodate quality, water is as solvent, and the weight ratio of the two is 1: 1.5～4.0.
Used sulfuric acid is and the whole salifiable amounts of cefpirome that the control pH value equals 1.0～1.5.
Separating out the crystalline temperature with ethanol is controlled at below 5 ℃.
The present invention is simple to operate, and the quality product that obtains is better, and yield is higher, and has avoided using bigger solvent such as the toluene of toxicity, has reduced three-waste pollution.
Embodiment
In order to remove contained oligopolymer, organism and harmful ion in the resin, to guarantee the activity of resin, it carries out pre-treatment and use after regenerating to need water and acid base pair in following examples.
Quality product is controlled by the high effective liquid chromatography for measuring related substance.Method is as follows:
Chromatographic condition and system suitability test are weighting agent with octadecylsilane chemically bonded silica, mix with ammonium phosphate solution-acetonitrile (8: 1), and transferring pH to 3.3～3.5 with triethylamine is moving phase, and the detection wavelength is 270nm.
It is an amount of that the cefpirome trial-product is got in the preparation of need testing solution, adds the solution that moving phase is made into 0.5mg/ml, promptly.
It is an amount of that the cefpirome reference substance is got in the preparation of reference substance solution, adds the solution that moving phase is made into 0.005mg/ml, promptly.
Assay method: get each 10 μ l of need testing solution and reference substance solution respectively and inject liquid chromatograph, measure and the record peak area, calculate the content of relative substance in the trial-product by external standard method.
Embodiment 1
In the 100ml reaction flask, add 10g cefpirome hydriodate, pretreated 201 * 7 type strongly basic anion exchange resin 30ml and deionized water 20ml, stirring at room to iodate hydrogen salt dissolves fully, filter, add gac 0.5g in the filtrate, stirred 30 minutes, filter, the aqueous solution is cooled to 5 ℃, transfers pH to 1.3 with 6N sulfuric acid, drip cold ethanol then, separate out white precipitate,, filter 5 ℃ of following insulated and stirred 2 hours, use cold washing with alcohol, get off-white color crystallization 5.5g after the vacuum-drying.Yield 68.8%.Relevant thing:＜2.0%
Embodiment 2
In the 100ml reaction flask, add 10g cefpirome hydriodate, pretreated D262 type strongly basic anion exchange resin 40ml and deionized water 30ml, stirring at room to iodate hydrogen salt dissolves fully, filter, add gac 0.5g in the filtrate, stirred 35 minutes, filter, the aqueous solution is cooled to 5 ℃, transfers pH to 1.3 with 6N sulfuric acid, drip cold ethanol then, separate out white precipitate,, filter 5 ℃ of following insulated and stirred 3 hours, use cold washing with alcohol, get off-white color crystallization 5.6g after the vacuum-drying.Yield 70.0%.Relevant thing:＜2.0%
Embodiment 3
In the 100ml reaction flask, add 10g cefpirome hydriodate, pretreated D201 type strongly basic anion exchange resin 40ml and deionized water 30ml, stirring at room to iodate hydrogen salt dissolves fully, filter, add gac 0.8g in the filtrate, stirred 25 minutes, filter, the aqueous solution is cooled to 5 ℃, transfers pH to 1.3 with 4N sulfuric acid, drip cold ethanol then, separate out white precipitate,, filter 5 ℃ of following insulated and stirred 2.5 hours, use cold washing with alcohol, get off-white color crystallization 5.1g after the vacuum-drying.Yield 63.8%.Relevant thing:＜2.0%
Embodiment 4
In the 100ml reaction flask, add 10g cefpirome hydriodate, pretreated D301R type weak base anion-exchange resin 25ml and deionized water 20ml, stirring at room to iodate hydrogen salt dissolves fully, filter, add gac 0.5g in the filtrate, stirred 30 minutes, filter, the aqueous solution is cooled to 5 ℃, transfers pH to 1.3 with 6N sulfuric acid, drip cold ethanol then, separate out white precipitate,, filter 5 ℃ of following insulated and stirred 2.5 hours, use cold washing with alcohol, get off-white color crystallization 5.3g after the vacuum-drying.Yield 66.3%.Relevant thing:＜2.0%
Embodiment 5
In the 100ml reaction flask, add 10g cefpirome hydriodate, pretreated D370 type weak base anion-exchange resin 40ml and deionized water 30ml, stirring at room to iodate hydrogen salt dissolves fully, filter, add gac 0.5g in the filtrate, stirred 20 minutes, filter, the aqueous solution is cooled to 5 ℃, transfers pH to 1.3 with 6N sulfuric acid, drip cold ethanol then, separate out white precipitate,, filter 5 ℃ of following insulated and stirred 2 hours, use cold washing with alcohol, get off-white color crystallization 4.9g after the vacuum-drying.Yield 61.3%.Relevant thing:＜2.0%
Embodiment 6
In the 100ml reaction flask, add 10g cefpirome hydriodate, pretreated D301G type weak base anion-exchange resin 30ml and deionized water 30ml, stirring at room to iodate hydrogen salt dissolves fully, filter, add gac 0.5g in the filtrate, stirred 25 minutes, filter, the aqueous solution is cooled to 5 ℃, transfers pH to 1.3 with 6N sulfuric acid, drip cold ethanol then, separate out white precipitate,, filter 5 ℃ of following insulated and stirred 3 hours, use cold washing with alcohol, get off-white color crystallization 5.0g after the vacuum-drying.Yield 62.5%.Relevant thing:＜2.0%.
Claims (8)
1. the preparation method of a Cefpirome Sulfate, it is characterized in that the cefpirome hydriodate handled under water as solvent with basic anion exchange resin and obtain cefpirome, with the sulfuric acid salify of sufficient quantity, add ethanol and separate out crystallization then, Cefpirome Sulfate.
2. according to the preparation method of the described Cefpirome Sulfate of claim 1, the mass volume ratio that it is characterized in that cefpirome hydriodate and basic anion exchange resin is 1: 1.5～5.0.
3. according to the preparation method of the described Cefpirome Sulfate of claim 1, it is characterized in that basic anion exchange resin selects strongly basic anion exchange resin and weak base anion-exchange resin for use.
4. according to the preparation method of the described Cefpirome Sulfate of claim 3, it is characterized in that strongly basic anion exchange resin selects that model is 201 * 2,201 * 8,202 * 7 for use, D261, D280, D284, D290, D296, D201GF, 201 * 7, D201, D262.
5. according to the preparation method of the described Cefpirome Sulfate of claim 3, it is characterized in that it is D301R, D301G, D370, D371, D380, D382, D392 that weak base anion-exchange resin is selected model for use.
6. according to the preparation method of the described Cefpirome Sulfate of claim 1, it is characterized in that in cefpirome hydriodate quality that water is as solvent, the weight ratio of the two is 1: 1.5～4.0.
7. according to the preparation method of the described Cefpirome Sulfate of claim 1, it is characterized in that used sulfuric acid is and the whole salifiable amounts of cefpirome, the pH value equals 1.0～1.5.
8. according to the preparation method of the described Cefpirome Sulfate of claim 1, it is characterized in that separating out the crystalline temperature with ethanol is controlled at below 5 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006101021195A CN101172982B (en) | 2006-11-03 | 2006-11-03 | Method of preparing cefpirome sulfate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006101021195A CN101172982B (en) | 2006-11-03 | 2006-11-03 | Method of preparing cefpirome sulfate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101172982A CN101172982A (en) | 2008-05-07 |
| CN101172982B true CN101172982B (en) | 2011-06-08 |
Family
ID=39421755
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2006101021195A Expired - Fee Related CN101172982B (en) | 2006-11-03 | 2006-11-03 | Method of preparing cefpirome sulfate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101172982B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044455B (en) * | 2011-10-17 | 2015-04-01 | 苏州中联化学制药有限公司 | Reworking method of cefpirome sulfate mixed powder |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4609653A (en) * | 1982-12-28 | 1986-09-02 | Hoechst Aktiengesellschaft | Crystalline cephem-acid addition salts and processes for their preparation |
| CN1587267A (en) * | 2004-06-29 | 2005-03-02 | 魏雪纹 | Process for synthesizing cefpirome sulfate |
| CN1772754A (en) * | 2005-11-04 | 2006-05-17 | 江西科技师范学院 | Synthesis process of cefpirome and its analog |
-
2006
- 2006-11-03 CN CN2006101021195A patent/CN101172982B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4609653A (en) * | 1982-12-28 | 1986-09-02 | Hoechst Aktiengesellschaft | Crystalline cephem-acid addition salts and processes for their preparation |
| CN1587267A (en) * | 2004-06-29 | 2005-03-02 | 魏雪纹 | Process for synthesizing cefpirome sulfate |
| CN1772754A (en) * | 2005-11-04 | 2006-05-17 | 江西科技师范学院 | Synthesis process of cefpirome and its analog |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101172982A (en) | 2008-05-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104860939A (en) | Cinchona alkaloids compound and preparation method thereof | |
| CN101172982B (en) | Method of preparing cefpirome sulfate | |
| CN101906109B (en) | Method for preparing cefuroxime sodium | |
| CN101337970B (en) | Method for synthesizing antibiotic cefpirome sulfate | |
| CN104892583A (en) | Copper ion Schiff-base probe compound and preparation thereof | |
| CN110078728B (en) | Abamebactam intermediate, preparation method and application thereof | |
| CN105820145A (en) | Method for preparing 5-nitro-2-furaldehyde and nifuratel | |
| CN105111188B (en) | A kind of preparation method of esomeprazole magnesium trihydrate crystal formation | |
| CN101781264B (en) | Production method of 1-methyl-5-mercapto-1,2,3,4-tetrazole | |
| CN104262361B (en) | Process for preparing ceftezole sodium | |
| CN101787038B (en) | Preparation method of cefquinome sulfate | |
| CN102061160A (en) | Synthesis process of fluorescent probe for detecting mercury ions | |
| CN103193800B (en) | A kind of method of each component of separation and purification from cefaclor enzymatic reaction liquid | |
| CN102391292B (en) | Polyamine copper complexes using rhodamine B as fluorescent marker and method for detecting nitric oxide by using polyamine copper complexes | |
| CN103772454B (en) | The process for purification of Clindamycin Phosphate | |
| CN110183519A (en) | A kind of isolation and purification method of Dalbavancin key intermediate A40926 | |
| CN102070540B (en) | 1-oxygen-2-(1-ethoxy)-3-methyl-quinoxaline, and preparation method and application thereof | |
| CN103374019A (en) | Preparation method of cefuroxlme sodium | |
| CN102329328A (en) | Novel method for purifying ceftizoxime sodium compound | |
| CN102993216A (en) | Preparation method of ceftiofur hydrochloride | |
| CN103030650A (en) | Method for preparing cefotiam hexetil and method for preparing cefotiam hexetil dihydrochloride | |
| CN103980293B (en) | 3-vinyl-7-(thiazole methoxyimino) preparation method of Cephalosporanic acid | |
| CN101270090B (en) | Method for preparing albendazole oxide | |
| CN114163361B (en) | Preparation method of 3-bromo-5-hydroxy benzene sulfonamide | |
| CN103275143B (en) | The new crystal �� of Clindamycin Phosphate and preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| DD01 | Delivery of document by public notice |
Addressee: Zhao Kai Document name: Notification of Termination of Patent Right |
|
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110608 Termination date: 20111103 |