CN1305876C - One-step method for preparing high-purity cefpoxime proxetil - Google Patents
One-step method for preparing high-purity cefpoxime proxetil Download PDFInfo
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- CN1305876C CN1305876C CNB2004100156938A CN200410015693A CN1305876C CN 1305876 C CN1305876 C CN 1305876C CN B2004100156938 A CNB2004100156938 A CN B2004100156938A CN 200410015693 A CN200410015693 A CN 200410015693A CN 1305876 C CN1305876 C CN 1305876C
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- Prior art keywords
- cefpodoxime
- acid
- potassium
- sodium
- proxetil
- Prior art date
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Abstract
The present invention belongs to the technical field of medicine synthesis. The present invention provides a one-step process for preparing high-purity cefpoxime proxetil form cefpoxime acid. The process of the present invention is simple and feasible, and is suitable for large-scale production. The product prepared by the process of the present invention is high in purity, and the content of the side product (cefpoxime proxetil isomer) (delta<2>) is lower than 1 %.
Description
Technical field
The invention belongs to technical field of medicine synthesis.Be specifically related to prepare the method for high purity Cefpodoxime Proxetil with Cefpodoxime acid.
Background technology
Cefpodoxime Proxetil Cefpodoxime proxetil, (R, S)-1-(isopropoxy carbon acyloxy) ethyl-(+)-(6R, 7R)-7-[2-(2-amino-4-thiazolyl)-2-((z)-methoxyimino) kharophen]-3-methoxymethyl-8-oxygen-5-sulphur-1-azabicyclo [4,2, O] oct-2-ene-2-carboxylicesters (I) is antibiotic wide spectrum, high stability to β-Nei Xiananmei, third generation oral cephalosporin medicine.
Document (J.of Antibiotics, Vol 40,370 (1987)) report, by make Cefpodoxime (II) in the presence of strong organic bases such as dicyclohexyl amine with iodine alkyl carbonate prepared in reaction Cefpodoxime Proxetil.The product that this method obtains, its by product is the isomer Δ especially
2Higher relatively, generally more than 3%.
World patent (WO01/34611) discloses the use crown ether and has made catalyzer, prepares Cefpodoxime Proxetil from cefpoxime proxetil.At first, need to use crown ether to prepare Cefpodoxime Proxetil, not only cost is higher, and the toxicity of crown ether is disadvantageous for last directly preparation finished product, simultaneously, if without crown ether, the isomer that forms will reach 6～8% (weight) scope, therefore defectiveness still in preparation.
Summary of the invention
Technical problem to be solved by this invention is to overcome above-mentioned weak point, a kind of easy method for preparing the high purity Cefpodoxime Proxetil of research and design.
The invention provides the method for preparing the high purity Cefpodoxime Proxetil with Cefpodoxime acid, this method is a raw material with Cefpodoxime (acid) II, with sodium acetate, Sodium Propionate, Sodium isooctanoate, potassium acetate, potassium propionate or isocaprylic acid potassium organic weak base reactant salt after, add iodo-ester III and directly obtain I.
Synthetic route:
R=CH
3, CH
3CH
2Or CH
3(CH
2)
3CH (C
2H
5)
M=Na or K.
The mol ratio of RCOOM used in the present invention and raw material II allows at 1～3 times.Temperature of reaction-5～25 ℃, reasonable temperature range is 0～10 ℃, impurity in products＜4%, yield 70～75%.
The Cefpodoxime Proxetil purity height that makes with the inventive method detects wherein Δ through the HPLC method
2Isomer is less than 1%.If use the separation sensitivity of the HPLC collection of illustrative plates of WO01/34611 patent disclosure, the present invention produces the isomer Δ
2Will be less than 0.5%, total impurities is less than 4%, and American Pharmacopeia USP26 stipulates relative substance＜6%.Illustrate that the product that the inventive method makes is better than USS.
Embodiment
Embodiment 1
With 20g (0.0468 mole) Cefpodoxime (acid) II, put among the 120ml DMA, stirring and dissolving, add 4.6g sodium acetate and 1g water, stirring at room reaction 30min is cooled to 5 ℃, adds 15g iodo-ester III, at 5～10 ℃ of reaction 1.5h, be poured into 200ml ethyl acetate and 100ml 5%NaHCO
3In the mixed solution, stir, tell organic phase, water 100ml ethyl acetate extraction, merge organic phase, wash secondary with saturated common salt, organic phase adds 10g anhydrous magnesium sulfate and 10g activated carbon decolorizing 30min, filter, be evaporated to 80g, add the 500ml isopropyl ether fast, the high degree of agitation after-filtration, vacuum-drying gets in vain to off-white powder 19g.(yield: 73%)
Embodiment 2
With 20g Cefpodoxime (acid) II, put among the 120ml DMA stirring and dissolving, add 8.5g Sodium isooctanoate stirring at room reaction 30min, be cooled to 5 ℃, add 16g iodo-ester III, at 5～10 ℃ of reaction 1.5h, be poured into 200ml ethyl acetate and 100ml 5%NaHCO
3In the mixed solution, stir, tell organic phase, water 100ml ethyl acetate extraction, merge organic phase, wash secondary with saturated common salt, organic phase adds 10g gac and 10g anhydrous magnesium sulfate decolouring 30min, filter, be evaporated to 80g, add the 500ml isopropyl ether fast, after the high degree of agitation, filter, vacuum-drying gets white to off-white powder 19.5g.(yield: 75%)
Claims (2)
1. method for preparing high purity Cefpodoxime Proxetil I with Cefpodoxime acid II, it is characterized in that this method is is raw material with Cefpodoxime acid II, with sodium acetate, Sodium Propionate, Sodium isooctanoate, potassium acetate, potassium propionate or isocaprylic acid potassium organic weak base reactant salt after, add iodo-ester III and directly obtain I;
Synthetic route:
R=CH
3, CH
3CH
2Or CH
3(CH
2)
3CH (C
2H
5)
M=Na or K.
2. a kind of method for preparing high purity Cefpodoxime Proxetil I with Cefpodoxime acid II according to claim 1 is characterized in that the mol ratio of wherein said organic weak base salt sodium acetate, Sodium Propionate, Sodium isooctanoate, potassium acetate, potassium propionate or isocaprylic acid potassium and Cefpodoxime acid II is 1～3: 1; Temperature of reaction is-5-25 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100156938A CN1305876C (en) | 2004-01-08 | 2004-01-08 | One-step method for preparing high-purity cefpoxime proxetil |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100156938A CN1305876C (en) | 2004-01-08 | 2004-01-08 | One-step method for preparing high-purity cefpoxime proxetil |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1640879A CN1640879A (en) | 2005-07-20 |
| CN1305876C true CN1305876C (en) | 2007-03-21 |
Family
ID=34868046
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100156938A Expired - Fee Related CN1305876C (en) | 2004-01-08 | 2004-01-08 | One-step method for preparing high-purity cefpoxime proxetil |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1305876C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102532165A (en) * | 2010-12-20 | 2012-07-04 | 广州白云山制药股份有限公司广州白云山制药总厂 | Preparation method for cefathiamidine crystals |
| CN103275102B (en) * | 2013-05-28 | 2014-07-09 | 四川省惠达药业有限公司 | Cefpodoxime proxetil compound as well as preparation method and medicinal composition thereof |
| CN106046024B (en) * | 2016-06-30 | 2019-01-15 | 齐鲁动物保健品有限公司 | A kind of preparation method of Cefpodoxime Proxetil |
| CN115093431B (en) * | 2022-06-15 | 2023-09-22 | 艾美科健（中国）生物医药有限公司 | Method for synthesizing cefpodoxime proxetil |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002083634A2 (en) * | 2001-04-17 | 2002-10-24 | Ranbaxy Laboratories Limited | Process for the preparation of cefpodoxime acid |
| CN1387533A (en) * | 1999-11-08 | 2002-12-25 | 韩美药品工业株式会社 | Method for prepairng highly purity cefpodoxime proxetil |
-
2004
- 2004-01-08 CN CNB2004100156938A patent/CN1305876C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1387533A (en) * | 1999-11-08 | 2002-12-25 | 韩美药品工业株式会社 | Method for prepairng highly purity cefpodoxime proxetil |
| WO2002083634A2 (en) * | 2001-04-17 | 2002-10-24 | Ranbaxy Laboratories Limited | Process for the preparation of cefpodoxime acid |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1640879A (en) | 2005-07-20 |
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|---|---|---|---|
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| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: SHANGHAI ZHONGXI SUNVE PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: SHANGHAI SUNVE PHARMACEUTICAL CO., LTD. |
|
| CP03 | Change of name, title or address |
Address after: 200331 No. 50, Yongdeng Road, Shanghai, China Patentee after: Shanghai Zhongxi Sunve Pharmaceutical Co., Ltd. Address before: 200331 No. 50, Yongdeng Road, Shanghai, Putuo District Patentee before: Shanghai Sunve Pharmaceutical Co., Ltd. |
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| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070321 Termination date: 20140108 |