CN102040597A - Improved production method of aztreonam - Google Patents
Improved production method of aztreonam Download PDFInfo
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- CN102040597A CN102040597A CN2009102048199A CN200910204819A CN102040597A CN 102040597 A CN102040597 A CN 102040597A CN 2009102048199 A CN2009102048199 A CN 2009102048199A CN 200910204819 A CN200910204819 A CN 200910204819A CN 102040597 A CN102040597 A CN 102040597A
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- aztreonam
- production method
- improved production
- tert
- filter
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Abstract
The invention describes an improved production method of aztreonam, comprising the following step: in the process of using strong acid to carry out hydrolysis on butyl aztreonam to generate the aztreonam, mixed solution of methyl alcohol and water is used as reaction medium. The aztreonam crystallization obtained by the method is easy to filter and dry.
Description
Technical field
The present invention relates to a kind of production method of improved aztreonam.
Background technology
Aztreonam shown in the molecular formula I (Aztreonam) is a kind of monocycle 3-lactam antibiotics of synthetic, and Gram-negative bacteria is had anti-microbial activity.
Some bibliographical informations the technology of preparing of aztreonam, for example: world patent WO2004013133 discloses by the aztreonam tert-butyl ester and has generated aztreonam in the heated in water solution hydrolysis of strong acid, cooled and filtered is also dry, obtains the aztreonam of alpha crystalline form.The crystallization that this method obtains is difficult for filtering and washing, becomes the knot lump in drying process easily.Cause labor strength big, the operating time is long, also has difficulties in next step treating process even hard blocky aztreonam is pulverized the back.
World patent WO2006122253 discloses the method for hydrolysis of the improved aztreonam tert-butyl ester, in inventive embodiments, obtain the aztreonam that wets after filtration by the aztreonam of separating out in the water, wet aztreonam and ammonium acetate mix the back and add dissolve with ethanol, with separating out aztreonam behind hydrochloric acid accent PH to 1～3, the aztreonam crystallization that obtains in this way is easy to filter and is dry, and dried product does not lump.But, must increase cost, but also cause yield losses owing to increased treatment step.
Purpose of the present invention will address these problems exactly.
Summary of the invention
The present invention relates to a kind of new production method, to improve the production method of aztreonam.
The present invention is described by the improvement of the aztreonam tert-butyl ester in the process of aqueous solution usefulness strong acid hydrolysis generation aztreonam to WO2004013133 and WO2006122253, reaction medium is improved to the mixing solutions of first alcohol and water by water.
The aztreonam tert-butyl ester can generate aztreonam with strong acid hydrolysis in the aqueous solution of heating, and the aztreonam that obtains is separated out with solid form.
The inventor is unexpected to be found, is being generated with the strong acid hydrolysis in the process of aztreonam by the aztreonam tert-butyl ester, and the mixing solutions that uses the first alcohol and water is as reaction medium, and the aztreonam crystallization that obtains is easy to filter and is dry.
Specifically, strong acid of the present invention refers to organic acid or inorganic acid, preferred trifluoroacetic acid or hydrochloric acid.
In the mixed solution used in the present invention, methanol concentration is 1% to 20%, and preferred concentration is 2% to 10%.
Aztreonam by the inventive method preparation is suitable for preparing anhydrous aztreonam, for example is dissolved in dehydrated alcohol under lower temperature, separates out anhydrous aztreonam through the Sterile Filtration post-heating.
Compared with former technology, major advantage of the present invention is that the aztreonam crystallization that obtains is easy to filter and is dry, therefore can reduce labour intensity, reduces operation steps, save cost, and quality product is better.
The raw materials used aztreonam tert-butyl ester of the present invention can be according to the described method preparation of WO2004013133.
Embodiment
Following non-limiting example will further specify the present invention.
Reference example 1
The 27 gram aztreonam tert-butyl esters are suspended in the mixed solution of 122 ml waters and 1.35 gram concentrated hydrochloric acids, suspension is heated to 60 ℃, add 30 milliliters of concentrated hydrochloric acids, keep 63 ℃ to 65 ℃ vigorous stirring reaction solutions, solid is molten clear in 15 minutes afterreaction liquid, and separate out white solid immediately, continue vigorous stirring reaction 15 minutes, add 162 milliliters of cold water, be cooled to 25 ℃ of insulations 2 hours, continue to be cooled to 0 ℃ of insulation 2 hours, filter, wash twice, wash twice with 125 milliliters of acetone making beating with 120 milliliters of cold water making beating, filter, keep 40 ℃ to 50 ℃ dryings to obtain 19.5 gram aztreonam in 8 hours.Moisture content is 15%.
In pulping process, aztreonam is very sticky, is difficult to making beating evenly, and dried product is Powdered, and grit is arranged.
Embodiment 1
The 27 gram aztreonam tert-butyl esters are suspended in the mixed solution of 110 ml waters and 1.35 gram concentrated hydrochloric acids, suspension is heated to 60 ℃, add 30 milliliters of concentrated hydrochloric acids and 10 ml methanol, keep 63 ℃ to 65 ℃ vigorous stirring reaction solutions, solid is molten clear in 12 minutes afterreaction liquid, and separate out white solid immediately, continue vigorous stirring reaction 15 minutes, add 162 milliliters of cold water, be cooled to 25 ℃ of insulations 2 hours, continue to be cooled to 0 ℃ of insulation 2 hours, filter, wash twice with 125 milliliters of acetone making beating, filter, keep 40 ℃ to 50 ℃ dryings to obtain 20 gram crystalloid aztreonam in 4 hours.Moisture content is 12%.
Claims (3)
1. the production method of aztreonam is included in by in the process of the aztreonam tert-butyl ester with strong acid hydrolysis generation aztreonam, and the mixing solutions that uses the first alcohol and water is as reaction medium.
2. the method for claims 1, wherein methanol concentration is 1% to 20%.
3. the method for claims 2, wherein methanol concentration is 2% to 10%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102048199A CN102040597A (en) | 2009-10-14 | 2009-10-14 | Improved production method of aztreonam |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102048199A CN102040597A (en) | 2009-10-14 | 2009-10-14 | Improved production method of aztreonam |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102040597A true CN102040597A (en) | 2011-05-04 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009102048199A Pending CN102040597A (en) | 2009-10-14 | 2009-10-14 | Improved production method of aztreonam |
Country Status (1)
| Country | Link |
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| CN (1) | CN102040597A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103570707A (en) * | 2012-07-21 | 2014-02-12 | 重庆圣华曦药业股份有限公司 | Improved synthetic method of aztreonam |
| CN105017241A (en) * | 2015-06-24 | 2015-11-04 | 山东罗欣药业集团股份有限公司 | Aztreonam compound and preparation thereof |
| CN105085511A (en) * | 2015-05-29 | 2015-11-25 | 石药集团中诺药业（石家庄）有限公司 | Novel aztreonam compound |
-
2009
- 2009-10-14 CN CN2009102048199A patent/CN102040597A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103570707A (en) * | 2012-07-21 | 2014-02-12 | 重庆圣华曦药业股份有限公司 | Improved synthetic method of aztreonam |
| CN103570707B (en) * | 2012-07-21 | 2016-03-09 | 重庆圣华曦药业股份有限公司 | A kind of synthetic method of aztreonam of improvement |
| CN105085511A (en) * | 2015-05-29 | 2015-11-25 | 石药集团中诺药业（石家庄）有限公司 | Novel aztreonam compound |
| CN105085511B (en) * | 2015-05-29 | 2018-04-06 | 石药集团中诺药业（石家庄）有限公司 | A kind of new aztreonam compound |
| CN105017241A (en) * | 2015-06-24 | 2015-11-04 | 山东罗欣药业集团股份有限公司 | Aztreonam compound and preparation thereof |
| CN105017241B (en) * | 2015-06-24 | 2018-03-06 | 山东罗欣药业集团股份有限公司 | A kind of aztreonam compound and its preparation |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| DD01 | Delivery of document by public notice |
Addressee: Guo Qingchun Document name: Notification of Passing Preliminary Examination of the Application for Invention |
|
| C06 | Publication | ||
| PB01 | Publication | ||
| DD01 | Delivery of document by public notice |
Addressee: Guo Qingchun Document name: Notification of Publication of the Application for Invention |
|
| DD01 | Delivery of document by public notice |
Addressee: Beijing Hecheng Xianfeng Pharmaceutical Technology Co., Ltd. Document name: Notification of before Expiration of Request of Examination as to Substance |
|
| DD01 | Delivery of document by public notice |
Addressee: Beijing Hecheng Xianfeng Pharmaceutical Technology Co., Ltd. Document name: Notification that Application Deemed to be Withdrawn |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110504 |