CN107056752A - A kind of preparation method of esomeprazole potassium - Google Patents
A kind of preparation method of esomeprazole potassium Download PDFInfo
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- CN107056752A CN107056752A CN201710214890.XA CN201710214890A CN107056752A CN 107056752 A CN107056752 A CN 107056752A CN 201710214890 A CN201710214890 A CN 201710214890A CN 107056752 A CN107056752 A CN 107056752A
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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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Abstract
The invention discloses a kind of preparation method of esomeprazole potassium：(1) toluene is put into dry reactor, nitrogen to centrifugation is passed through into toluene and is terminated；(2) Omeprazole thioether is put into, 30~32 DEG C, input D () ethyl tartrate 26Kg are warming up to；(3) 44~46 DEG C are warming up to, stirring puts into isopropyl titanate (IV) after 30 minutes；(4) 31~35 DEG C are cooled to, diisopropylethylamine is put into；(5) keeping temperature is 31~33 DEG C, in cumyl hydroperoxide is added dropwise in 30 minutes~2 hours；(6) in 31~33 DEG C of insulation reactions 15 minutes；QC checks whether sulfide content monitoring reaction terminates after (7) reaction terminates, the methanol solution of the lower potassium hydroxide of stirring；(8) 25~30 DEG C are cooled to and is kept for 1 hour；(9) centrifuge, obtain crude product and go forward side by side an one-step refining.
Description
Technical field
The present invention relates to a kind of preparation method of esomeprazole potassium, belong to pharmaceutical field.
Background technology
Esomeprazole magnesium also known as levo-omeprazole, Esso he draw azoles, chemical name (S)-(-) -5- methoxyl groups -2-
{ [(4- methoxyl group -3,5- dimethyl -2- pyridine radicals) methyl] sulfinyl } -1H- benzimidazole magnesium salts, is that marketed products are difficult to understand
The magnesium salts preparation of (S)-(-)-type single enantiomer of azoles draws in U.S., is researched and developed by Astra Zeneca companies of Sweden, 2004 at me
State lists；It is a kind of new proton pump inhibitor, H+/K+-ATP enzymatic activitys can be suppressed, clinic is mainly used in treating gastric acid secretion
The disease of digestive system such as gastric ulcer, duodenal ulcer and reflux esophagitis caused by excessive.
The esomeprazole magnesium intermediate esomeprazole that patent US6369085B1 (patent families WO9854171A) is announced
The preparation method of potassium is：Water and D- (-) ethyl tartrate are added into the toluene solution of Omeprazole thioether, 50 are warming up to
DEG C, stir 20 minutes, then add isopropyl titanate (IV), stirred 45 minutes at 50 DEG C；30 DEG C are cooled to, diisopropyl second is added
Amine, is maintained at 28~34 DEG C of dropwise addition cumyl hydroperoxides, and completion of dropping is warming up to 35 DEG C, and reaction adds potassium methoxide after 2 hours
Methanol solution, after 14 hours filter, wash, dry after esomeprazole potassium.Yield 74%, content 89%.
Patent CN105418588A discloses a kind of entirely different chiral systems and prepares esomeprazole potassium, i.e., 30~
At 55 DEG C, by Omeprazole thioether, (R) -1,1 '-dinaphthalene -2,2 '-diamines, inorganic metal salt are mixed in acetone, stirring 0.5
15~45 DEG C are cooled to after~2 hours, 30% hydrogen peroxide is then instilled and carries out oxidation reaction, reaction adds hydroxide after terminating
Potassium methanol solution, obtains esomeprazole potassium.
Esso esomeprazole potassium is prepared by the patent US6369085B1 methods described, yield and purity are relatively low, and thioether
Easy over oxidation is higher into sulfone, R- enantiomers.
It is contemplated that developing the few Esso esomeprazole potassium production technology of a kind of high income, Functionality, quality and appealing design, impurity.
The content of the invention
In view of the shortcomings of the prior art, the present invention relates to the few Esso esomeprazole of a kind of high income, Functionality, quality and appealing design, impurity
Potassium production technology.
A kind of preparation method of esomeprazole potassium, its step is as follows：
(1) 1200L toluene is put into dry reactor, nitrogen to centrifugation is passed through into toluene and is terminated；
(2) 300Kg Omeprazole thioethers are put into, 30~32 DEG C are warming up to, D- (-) ethyl tartrate 26Kg is put into；
(3) 44~46 DEG C are warming up to, stirring puts into 16Kg isopropyl titanates (IV) after 30 minutes；
(4) 31~35 DEG C are cooled to, 12Kg diisopropylethylamine is put into；
(5) keeping temperature is 31~33 DEG C, in dropwise addition 180Kg cumyl hydroperoxides in 30 minutes~2 hours；
(6) in 31~33 DEG C of insulation reactions 15 minutes；
QC checks sulfide content (limit：It must not cross whether 5.0%) monitoring reaction terminates
(7) after reaction terminates, the methanol solution (66kg potassium hydroxide+300L methanol) of the lower potassium hydroxide of stirring；
(8) 25~30 DEG C are cooled to and is kept for 1 hour；
(9) centrifuge, obtain crude product.
It is refined:
(10) gained crude product is dissolved in 1000L water, stirring makes to be completely dissolved, stands 30 minutes；
(11) organic phase is separated, 1000L dichloromethane is put into, with vinegar acid for adjusting pH value to 7.5~8.0；
(12) dichloromethane layer is separated after standing 30 minutes, 30 minutes are stood after putting into 100L dichloromethane, 15 points of stirring；
(13) organic phase is separated, the methanol solution (46Kg potassium hydroxide+120L methanol) of potassium hydroxide is put into, 10 points are stirred
Clock；
(14) 20~25 DEG C are cooled to；
(15) transfer organic phase is stirred 15 minutes to reactor；
(16) dichloromethane is distilled off less than 42 DEG C
(17) 560L methanol is put into, stirring is to slowly warm up to 50~55 DEG C after 30 minutes, kept for 15~20 minutes；
(20) 30~35 DEG C are cooled to, centrifugation, spin are dried 20~30 minutes；
(19) washed with 40L methanol, spin is dried 20~30 minutes；
Yield：87%~90%.Purity >=95.0%, R- enantiomer≤1.5%.
Advantages of the present invention：
The technique of the present invention is simply operated well, and cost is low, and effect is good：Product yield is higher, and purity is higher, R- enantiomers
It is few, it is simple to operate, beneficial to commercially producing.
Embodiment
Embodiments of the invention are described below in detail, the embodiment is only used for explaining the present invention, and it is not intended that right
The limitation of the present invention.
The specific embodiment of the present invention is as described below.
Embodiment 1
A kind of preparation method of esomeprazole potassium, its step is as follows：
(1) 1200L toluene is put into dry reactor, nitrogen to centrifugation is passed through into toluene and is terminated；
(2) 300Kg Omeprazole thioethers are put into, 30~32 DEG C are warming up to, D- (-) ethyl tartrate 26Kg is put into；
(3) 44~46 DEG C are warming up to, stirring puts into 16Kg isopropyl titanates (IV) after 30 minutes；
(4) 31~35 DEG C are cooled to, 12Kg diisopropylethylamine is put into；
(5) keeping temperature is 31~33 DEG C, in dropwise addition 180Kg cumyl hydroperoxides in 30 minutes~2 hours；
(6) in 31~33 DEG C of insulation reactions 15 minutes；
QC checks sulfide content (limit：It must not cross whether 5.0%) monitoring reaction terminates
(7) after reaction terminates, the methanol solution (66kg potassium hydroxide+300L methanol) of the lower potassium hydroxide of stirring；
(8) 25~30 DEG C are cooled to and is kept for 1 hour；
(9) centrifuge, obtain crude product.
It is refined:
(10) gained crude product is dissolved in 1000L water, stirring makes to be completely dissolved, stands 30 minutes；
(11) organic phase is separated, 1000L dichloromethane is put into, with vinegar acid for adjusting pH value to 7.5~8.0；
(12) dichloromethane layer is separated after standing 30 minutes, 30 minutes are stood after putting into 100L dichloromethane, 15 points of stirring；
(13) organic phase is separated, the methanol solution (46Kg potassium hydroxide+120L methanol) of potassium hydroxide is put into, 10 points are stirred
Clock；
(14) 20~25 DEG C are cooled to；
(15) transfer organic phase is stirred 15 minutes to reactor；
(16) dichloromethane is distilled off less than 42 DEG C
(17) 560L methanol is put into, stirring is to slowly warm up to 50~55 DEG C after 30 minutes, kept for 15~20 minutes；
(18) 30~35 DEG C are cooled to, centrifugation, spin are dried 20~30 minutes；
(19) washed with 40L methanol, spin is dried 20~30 minutes；
Yield：87%~90%.
Purity >=95.0%, R- enantiomer≤1.5%.
Embodiment 2
A kind of preparation method of esomeprazole potassium, its step is as follows：
(1) 1200L toluene is put into dry reactor, nitrogen to centrifugation is passed through into toluene and is terminated；
(2) 300Kg Omeprazole thioethers are put into, 30~32 DEG C are warming up to, D- (-) ethyl tartrate 26Kg is put into；
(3) 44~46 DEG C are warming up to, stirring puts into 16Kg isopropyl titanates (IV) after 30 minutes；
(4) 31~35 DEG C are cooled to, 12Kg diisopropylethylamine is put into；
(5) keeping temperature is 31~33 DEG C, in dropwise addition 180Kg cumyl hydroperoxides in 30 minutes~2 hours；
(6) in 31~33 DEG C of insulation reactions 15 minutes；
QC checks sulfide content (limit：It must not cross whether 5.0%) monitoring reaction terminates
(7) after reaction terminates, the methanol solution (66kg potassium hydroxide+300L methanol) of the lower potassium hydroxide of stirring；
(8) 25~30 DEG C are cooled to and is kept for 1 hour；
(9) centrifuge, obtain crude product.
It is refined:
(10) gained crude product is dissolved in 1000L water, stirring makes to be completely dissolved, stands 30 minutes；
(11) organic phase is separated, 1000L dichloromethane is put into, with vinegar acid for adjusting pH value to 7.5~8.0；
(12) dichloromethane layer is separated after standing 30 minutes, 30 minutes are stood after putting into 100L dichloromethane, 15 points of stirring；
(13) organic phase is separated, the methanol solution (46Kg potassium hydroxide+120L methanol) of potassium hydroxide is put into, 10 points are stirred
Clock；
(14) 20~25 DEG C are cooled to；
(15) transfer organic phase is stirred 15 minutes to reactor；
(16) dichloromethane is distilled off less than 42 DEG C
(17) 560L methanol is put into, stirring is to slowly warm up to 50~55 DEG C after 30 minutes, kept for 15~20 minutes；
(18) 30~35 DEG C are cooled to, centrifugation, spin are dried 20~30 minutes；
(19) washed with 40L methanol, spin is dried 20~30 minutes；
Yield：87%~90%.
Purity >=95.0%, R- enantiomer≤1.5%.
Embodiment 3：
A kind of preparation method of esomeprazole potassium, its step is as follows：
(1) 1200L toluene is put into dry reactor, nitrogen to centrifugation is passed through into toluene and is terminated；
(2) 300Kg Omeprazole thioethers are put into, 30~32 DEG C are warming up to, D- (-) ethyl tartrate 26Kg is put into；
(3) 44~46 DEG C are warming up to, stirring puts into 16Kg isopropyl titanates (IV) after 30 minutes；
(4) 31~35 DEG C are cooled to, 12Kg diisopropylethylamine is put into；
(5) keeping temperature is 31~33 DEG C, in dropwise addition 180Kg cumyl hydroperoxides in 30 minutes~2 hours；
(6) in 31~33 DEG C of insulation reactions 15 minutes；
QC checks sulfide content (limit：It must not cross whether 5.0%) monitoring reaction terminates
(7) after reaction terminates, the methanol solution (66kg potassium hydroxide+300L methanol) of the lower potassium hydroxide of stirring；
(8) 25~30 DEG C are cooled to and is kept for 1 hour；
(9) centrifuge, obtain crude product.
It is refined:
(10) gained crude product is dissolved in 1000L water, stirring makes to be completely dissolved, stands 30 minutes；
(11) organic phase is separated, 1000L dichloromethane is put into, with vinegar acid for adjusting pH value to 7.5~8.0；
(12) dichloromethane layer is separated after standing 30 minutes, 30 minutes are stood after putting into 100L dichloromethane, 15 points of stirring；
(13) organic phase is separated, the methanol solution (46Kg potassium hydroxide+120L methanol) of potassium hydroxide is put into, 10 points are stirred
Clock；
(14) 20~25 DEG C are cooled to；
(15) transfer organic phase is stirred 15 minutes to reactor；
(16) dichloromethane is distilled off less than 42 DEG C
(17) 560L methanol is put into, stirring is to slowly warm up to 50~55 DEG C after 30 minutes, kept for 15~20 minutes；
(18) 30~35 DEG C are cooled to, centrifugation, spin are dried 20~30 minutes；
(19) washed with 40L methanol, spin is dried 20~30 minutes；
Yield：87%~90%.
Purity >=95.0%, R- enantiomer≤1.5%.
Embodiment 4
A kind of preparation method of esomeprazole potassium, its step is as follows：
(1) 1200L toluene is put into dry reactor, nitrogen to centrifugation is passed through into toluene and is terminated；
(2) 300Kg Omeprazole thioethers are put into, 30~32 DEG C are warming up to, D- (-) ethyl tartrate 26Kg is put into；
(3) 44~46 DEG C are warming up to, stirring puts into 16Kg isopropyl titanates (IV) after 30 minutes；
(4) 31~35 DEG C are cooled to, 12Kg diisopropylethylamine is put into；
(5) keeping temperature is 31~33 DEG C, in dropwise addition 180Kg cumyl hydroperoxides in 30 minutes~2 hours；
(6) in 31~33 DEG C of insulation reactions 15 minutes；
QC checks sulfide content (limit：It must not cross whether 5.0%) monitoring reaction terminates
(7) after reaction terminates, the methanol solution (66kg potassium hydroxide+300L methanol) of the lower potassium hydroxide of stirring；
(8) 25~30 DEG C are cooled to and is kept for 1 hour；
(9) centrifuge, obtain crude product.
It is refined:
(10) gained crude product is dissolved in 1000L water, stirring makes to be completely dissolved, stands 30 minutes；
(11) organic phase is separated, 1000L dichloromethane is put into, with vinegar acid for adjusting pH value to 7.5~8.0；
(12) dichloromethane layer is separated after standing 30 minutes, 30 minutes are stood after putting into 100L dichloromethane, 15 points of stirring；
(13) organic phase is separated, the methanol solution (46Kg potassium hydroxide+120L methanol) of potassium hydroxide is put into, 10 points are stirred
Clock；
(14) 20~25 DEG C are cooled to；
(15) transfer organic phase is stirred 15 minutes to reactor；
(16) dichloromethane is distilled off less than 42 DEG C
(17) 560L methanol is put into, stirring is to slowly warm up to 50~55 DEG C after 30 minutes, kept for 15~20 minutes；
(18) 30~35 DEG C are cooled to, centrifugation, spin are dried 20~30 minutes；
(19) washed with 40L methanol, spin is dried 20~30 minutes；
Yield：87%~90%.
Purity >=95.0%, R- enantiomer≤1.5%.
Embodiment 5
A kind of preparation method of esomeprazole potassium, its step is as follows：
(1) 1200L toluene is put into dry reactor, nitrogen to centrifugation is passed through into toluene and is terminated；
(2) 300Kg Omeprazole thioethers are put into, 30~32 DEG C are warming up to, D- (-) ethyl tartrate 26Kg is put into；
(3) 44~46 DEG C are warming up to, stirring puts into 16Kg isopropyl titanates (IV) after 30 minutes；
(4) 31~35 DEG C are cooled to, 12Kg diisopropylethylamine is put into；
(5) keeping temperature is 31~33 DEG C, in dropwise addition 180Kg cumyl hydroperoxides in 30 minutes~2 hours；
(6) in 31~33 DEG C of insulation reactions 15 minutes；
QC checks sulfide content (limit：It must not cross whether 5.0%) monitoring reaction terminates
(7) after reaction terminates, the methanol solution (66kg potassium hydroxide+300L methanol) of the lower potassium hydroxide of stirring；
(8) 25~30 DEG C are cooled to and is kept for 1 hour；
(9) centrifuge, obtain crude product.
It is refined:
(10) gained crude product is dissolved in 1000L water, stirring makes to be completely dissolved, stands 30 minutes；
(11) organic phase is separated, 1000L dichloromethane is put into, with vinegar acid for adjusting pH value to 7.5~8.0；
(12) dichloromethane layer is separated after standing 30 minutes, 30 minutes are stood after putting into 100L dichloromethane, 15 points of stirring；
(13) organic phase is separated, the methanol solution (46Kg potassium hydroxide+120L methanol) of potassium hydroxide is put into, 10 points are stirred
Clock；
(14) 20~25 DEG C are cooled to；
(15) transfer organic phase is stirred 15 minutes to reactor；
(16) dichloromethane is distilled off less than 42 DEG C
(17) 560L methanol is put into, stirring is to slowly warm up to 50~55 DEG C after 30 minutes, kept for 15~20 minutes；
(18) 30~35 DEG C are cooled to, centrifugation, spin are dried 20~30 minutes；
(19) washed with 40L methanol, spin is dried 20~30 minutes；
Yield：87%~90%.
Purity >=95.0%, R- enantiomer≤1.5%.
It should be noted that the preferred specific embodiment of the present invention is the foregoing is only,
If conception under this invention changes, its function produced, the spirit still covered without departing from specification
When, all should be within the scope of the invention.
In the description of this specification, reference term " one embodiment ", " some embodiments ", " example ", " specifically show
The description of example " or " some examples " etc. means to combine specific features, structure, material or the spy that the embodiment or example are described
Point is contained at least one embodiment of the present invention or example.In this manual, to the schematic representation of above-mentioned term not
Necessarily refer to identical embodiment or example.Moreover, specific features, structure, material or the feature of description can be any
One or more embodiments or example in combine in an appropriate manner.
Although an embodiment of the present invention has been shown and described, it will be understood by those skilled in the art that：Not
In the case of departing from the principle and objective of the present invention a variety of change, modification, replacement and modification can be carried out to these embodiments, this
The scope of invention is limited by claim and its equivalent.
Claims (3)
1. a kind of preparation method of esomeprazole potassium, its step is as follows：
(1) toluene is put into dry reactor, nitrogen to centrifugation is passed through into toluene and is terminated；
(2) Omeprazole thioether is put into, 30~32 DEG C are warming up to, D- (-) ethyl tartrate 26Kg is put into；
(3) 44~46 DEG C are warming up to, stirring puts into isopropyl titanate (IV) after 30 minutes；
(4) 31~35 DEG C are cooled to, diisopropylethylamine is put into；
(5) keeping temperature is 31~33 DEG C, in cumyl hydroperoxide is added dropwise in 30 minutes~2 hours；
(6) in 31~33 DEG C of insulation reactions 15 minutes；
QC checks whether sulfide content monitoring reaction terminates
(7) after reaction terminates, the methanol solution of the lower potassium hydroxide of stirring；
(8) 25~30 DEG C are cooled to and is kept for 1 hour；
(9) centrifuge, obtain crude product；
It is refined:
(10) gained crude product is soluble in water, stirring makes to be completely dissolved, and stands 30 minutes；
(11) organic phase is separated, dichloromethane is put into, with vinegar acid for adjusting pH value to 7.5~8.0；
(12) dichloromethane layer is separated after standing 30 minutes, 30 minutes are stood after putting into dichloromethane, 15 points of stirring；
(13) organic phase is separated, the methanol solution of potassium hydroxide is put into, stirred 10 minutes；
(14) 20~25 DEG C are cooled to；
(15) transfer organic phase is stirred 15 minutes to reactor；
(16) dichloromethane is distilled off less than 42 DEG C
(17) methanol is put into, stirring is to slowly warm up to 50~55 DEG C after 30 minutes, kept for 15~20 minutes；
(18) 30~35 DEG C are cooled to, centrifugation, spin are dried 20~30 minutes；
(19) washed with methanol, spin is dried 20~30 minutes.
2. the method described in claim 1, it is characterised in that：
A kind of preparation method of esomeprazole potassium, its step is as follows：
The methanol solution of potassium hydroxide is in step (7)：66kg potassium hydroxide+300L methanol.
3. the method described in claim 1 or 2, it is characterised in that step is as follows：
(1) 1200L toluene is put into dry reactor, nitrogen to centrifugation is passed through into toluene and is terminated；
(2) 300Kg Omeprazole thioethers are put into, 30~32 DEG C are warming up to, D- (-) ethyl tartrate 26Kg is put into；
(3) 44~46 DEG C are warming up to, stirring puts into 16Kg isopropyl titanates (IV) after 30 minutes；
(4) 31~35 DEG C are cooled to, 12Kg diisopropylethylamine is put into；
(5) keeping temperature is 31~33 DEG C, in dropwise addition 180Kg cumyl hydroperoxides in 30 minutes~2 hours；
(6) in 31~33 DEG C of insulation reactions 15 minutes；
QC checks sulfide content (limit：It must not cross whether 5.0%) monitoring reaction terminates
(7) after reaction terminates, the methanol solution (66kg potassium hydroxide+300L methanol) of the lower potassium hydroxide of stirring；
(8) 25~30 DEG C are cooled to and is kept for 1 hour；
(9) centrifuge, obtain crude product.
It is refined:
(10) gained crude product is dissolved in 1000L water, stirring makes to be completely dissolved, stands 30 minutes；
(11) organic phase is separated, 1000L dichloromethane is put into, with vinegar acid for adjusting pH value to 7.5~8.0；
(12) dichloromethane layer is separated after standing 30 minutes, 30 minutes are stood after putting into 100L dichloromethane, 15 points of stirring；
(13) organic phase is separated, the methanol solution (46Kg potassium hydroxide+120L methanol) of potassium hydroxide is put into, stirred 10 minutes；
(14) 20~25 DEG C are cooled to；
(15) transfer organic phase is stirred 15 minutes to reactor；
(16) dichloromethane is distilled off less than 42 DEG C
(17) 560L methanol is put into, stirring is to slowly warm up to 50~55 DEG C after 30 minutes, kept for 15~20 minutes；
(19) 30~35 DEG C are cooled to, centrifugation, spin are dried 20~30 minutes；
(19) washed with 40L methanol, spin is dried 20~30 minutes.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110229141A (en) * | 2019-06-20 | 2019-09-13 | 福安药业集团重庆博圣制药有限公司 | A kind of novel preparation method of high-purity esomeprazole sodium |
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| WO2003089408A2 (en) * | 2002-04-22 | 2003-10-30 | Sun Pharmaceutical Industries Limited | Optically active substituted pyridinylmethyl-sulphinyl-benzimidazole and salts |
| CN103570686A (en) * | 2013-10-14 | 2014-02-12 | 哈药集团技术中心 | Method for synthesizing and refining esomeprazole sodium |
| CN103694223A (en) * | 2013-07-03 | 2014-04-02 | 河南新帅克制药股份有限公司 | Method for preparing esomeprazole by one-pot method |
| CN103936715A (en) * | 2014-04-17 | 2014-07-23 | 哈尔滨珍宝制药有限公司 | Refining method and synthesis method of esomeprazole |
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- 2017-04-01 CN CN201710214890.XA patent/CN107056752A/en active Pending
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| WO2003089408A2 (en) * | 2002-04-22 | 2003-10-30 | Sun Pharmaceutical Industries Limited | Optically active substituted pyridinylmethyl-sulphinyl-benzimidazole and salts |
| CN103694223A (en) * | 2013-07-03 | 2014-04-02 | 河南新帅克制药股份有限公司 | Method for preparing esomeprazole by one-pot method |
| CN103570686A (en) * | 2013-10-14 | 2014-02-12 | 哈药集团技术中心 | Method for synthesizing and refining esomeprazole sodium |
| CN103936715A (en) * | 2014-04-17 | 2014-07-23 | 哈尔滨珍宝制药有限公司 | Refining method and synthesis method of esomeprazole |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110229141A (en) * | 2019-06-20 | 2019-09-13 | 福安药业集团重庆博圣制药有限公司 | A kind of novel preparation method of high-purity esomeprazole sodium |
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