CN107759567A - A kind of purification process of Esomeprazole sodium - Google Patents
A kind of purification process of Esomeprazole sodium Download PDFInfo
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- CN107759567A CN107759567A CN201610695989.1A CN201610695989A CN107759567A CN 107759567 A CN107759567 A CN 107759567A CN 201610695989 A CN201610695989 A CN 201610695989A CN 107759567 A CN107759567 A CN 107759567A
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- esomeprazole sodium
- purification process
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- crude product
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to pharmaceutical synthesis field, is related to a kind of purification process of Esomeprazole sodium, Esomeprazole sodium crude product is added to the water into dissolving, 0~18 DEG C stands 1~3 day, separates out colourless transparent crystal；Filter, washed using 0~5 DEG C of frozen water top；Vacuum drying, obtains high-purity esomeprazole sodium.The corresponding purifying process using water as solvent of the present invention is used, purity HPLC purity is brought up to 98 98.4%, has obtained the Esomeprazole sodium of high-purity；The inventive method is simple simultaneously, control condition is gentle, low production cost, pollution that organic solvent-free is brought, clean environment firendly, is especially suitable for large-scale industrial production.
Description
Technical field
The present invention relates to a kind of purification process, and in particular to a kind of purification process of Esomeprazole sodium.
Background technology
Esomeprazole is the S- isomers of Omeprazole, is first intravenous route administration that can be used for clinic in the world
Isomers proton pump inhibitor, its effect is stronger.Preclinical test shows that the anti-gastric acid secretion of esomeprazole, antiulcer are made
Omeprazole is obviously stronger than that with anti-helicobactor pylori activity；Clinical test shows the acid suppression positive effect of Esomeprazole sodium
It is better than Omeprazole, Lansoprazole and Pantoprazole.
At present, the synthetic method report about Esomeprazole sodium is more, as CN103087048A discloses a kind of Esso
The purification process of azoles sodium draws in U.S., after Esomeprazole sodium crude product is dissolved with 0.5~10 times of alcohols solvent, adds poor solvent,
Filtering, obtain solid and carry out dissolving crystallization with the acetone of 0.5~10 times of amount again, after system muddiness, add poor solvent, mistake
Filter, drying finally obtain sample.This method can remove a large amount of residual solvents that prior art is difficult to remove, obtain high-purity,
Low residual molten, in high yield product, suitable industrialized production.The present invention is surprised to find that a kind of new Esomeprazole sodium purifying side
Method, it is not necessary to introduce organic solvent, that is, obtain the Esomeprazole sodium of high-purity, and technique is simple, cost is low.
The content of the invention
It is an object of the invention to provide a kind of purification process of Esomeprazole sodium, and the purification process is simple, cost is low
Honest and clean, obtained Esomeprazole sodium impurity content is low, purity is high.
The purpose of the present invention is achieved by the following technical solution：
A kind of purification process of Esomeprazole sodium, it is characterised in that：
（1）Esomeprazole sodium crude product is added to the water dissolving, 0~10 DEG C stands 1~3 day, separates out colourless transparent crystal；
（2）Filter, washed using 0~5 DEG C of frozen water top；
（3）Vacuum drying, obtains high-purity esomeprazole sodium.
In order to which fully Esomeprazole sodium soluble in water is separated out, above-mentioned steps（1）Middle Esomeprazole sodium crude product with
The mass volume ratio of water（g/ml）Preferably 1：2-3, more preferably 1：3；Above-mentioned steps（1）In dwell temperature be preferably
5~10 DEG C, more preferably 9 DEG C.
In order to further improve the purity of final Esomeprazole sodium, above-mentioned steps（2）In using 2~4 DEG C of ice
Water, more preferably 3 DEG C；The frozen water and crude product volume mass ratio（ml/g）Preferably 5~6：1.
It is further preferred that above-mentioned steps（3）Vacuum drying temperature be 26~28 DEG C, the time be 4~5h.
Specifically, a kind of purification process of Esomeprazole sodium, is carried out as follows：
（1）, Esomeprazole sodium crude product is soluble in water, 9 DEG C stand 26~28 hours, colourless transparent crystal separate out；Described angstrom
The mass volume ratio of Suo Meila azoles sodium crude products and water（g/ml）For 1：3；
（2）, by the filtering of above-mentioned gained colourless transparent crystal, add frozen water top and wash；The volume mass ratio of the frozen water and crude product
（ml/g）For 5~6：1, the frozen water temperature is 3 DEG C；
（3）, again through 26~28 DEG C vacuum drying 4~5h, obtain high-purity esomeprazole sodium.
The present invention has following beneficial effect：
Those skilled in the art are not difficult to learn, Esomeprazole sodium is water-soluble very well, meets water is dissolved into rapidly solution, therefore can
Think with water to be that solvent is unworkable to Esomeprazole sodium crystallization purifying.Inventor was also once using along common thinking
Organic solvent purifies to Esomeprazole sodium, and has done substantial amounts of experimental study, constantly explored various step and technique bars
Part, but the purity of final gained Esomeprazole sodium does not reach desirable.Inventor is once accidental in long term test
It was found that using the corresponding purifying process using water as solvent of the present invention, purity is brought up into HPLC purity 98-98.4%, obtained
The Esomeprazole sodium of high-purity；The inventive method is simple simultaneously, control condition is gentle, low production cost, without organic molten
Pollution that agent is brought, clean environment firendly, are especially suitable for large-scale industrial production.
Embodiment
The present invention is further specifically described below by embodiment.It is necessarily pointed out that following examples
It is served only for that the present invention is further described, it is impossible to be interpreted as limiting the scope of the invention, the technology people in the field
Member can make some nonessential modifications and adaptations according to the invention described above content to the present invention.
Embodiment 1
The purifying of Esomeprazole sodium
By the 2 milliliters of dissolvings of 1 gram of Esomeprazole sodium crude product plus water, in 9 DEG C it is static place 28 hours, separate out colourless transparent crystal,
Filtering, 3 DEG C of addition, 5ml frozen water top are washed, and 26~28 DEG C of 4~5h of vacuum drying, obtain 0.7 gram of colourless crystallization object, HPLC purity
98.4%。
Embodiment 2
The purifying of Esomeprazole sodium sodium
Esomeprazole sodium crude product 1kg is added into the dissolving of 3 liters of water, in 8 DEG C it is static place 25 hours, separate out colourless transparent crystal, mistake
Filter, 5 DEG C of addition, 6 liters of 0 DEG C of frozen water tops are washed, and 30 DEG C of vacuum drying 4h, obtain colourless crystallization object 0.6kg, HPLC purity 98.3%.
Claims (6)
- A kind of 1. purification process of Esomeprazole sodium, it is characterised in that：（1）, Esomeprazole sodium crude product is added to the water it is molten Solution, 0~10 DEG C stands 1~3 day, separates out colourless transparent crystal；（2）Filter, washed using 0~5 DEG C of frozen water top；（3）, vacuum does It is dry, obtain high-purity esomeprazole sodium.
- 2. purification process as claimed in claim 1, it is characterised in that：The step（1）Middle Esomeprazole sodium crude product and water Mass volume ratio（g/ml）For 1：2~3, the dwell temperature is 5~15 DEG C.
- 3. purification process as claimed in claim 2, it is characterised in that：The step（1）Middle Esomeprazole sodium crude product and water Mass volume ratio（g/ml）For 1：3, the dwell temperature is 11 DEG C.
- 4. the purification process as described in claim 1,2 or 3, it is characterised in that：The step（2）In using 2~4 DEG C Frozen water.
- 5. purification process as claimed in claim 4, it is characterised in that：The step（2）In using 2 DEG C of frozen water.
- 6. the purification process as described in claim 1~6, it is characterised in that：The step（3）Vacuum drying temperature for 26~ 28 DEG C, the time be 4~5h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610695989.1A CN107759567A (en) | 2016-08-22 | 2016-08-22 | A kind of purification process of Esomeprazole sodium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610695989.1A CN107759567A (en) | 2016-08-22 | 2016-08-22 | A kind of purification process of Esomeprazole sodium |
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| Publication Number | Publication Date |
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| CN107759567A true CN107759567A (en) | 2018-03-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610695989.1A Pending CN107759567A (en) | 2016-08-22 | 2016-08-22 | A kind of purification process of Esomeprazole sodium |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110615860A (en) * | 2018-06-20 | 2019-12-27 | 江苏恒瑞医药股份有限公司 | Method for purifying sugammadex sodium |
-
2016
- 2016-08-22 CN CN201610695989.1A patent/CN107759567A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110615860A (en) * | 2018-06-20 | 2019-12-27 | 江苏恒瑞医药股份有限公司 | Method for purifying sugammadex sodium |
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180306 |
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| WD01 | Invention patent application deemed withdrawn after publication |