CN107488161A - A kind of light method for transformation of olopatadine N-butyl isomers - Google Patents
A kind of light method for transformation of olopatadine N-butyl isomers Download PDFInfo
- Publication number
- CN107488161A CN107488161A CN201610412887.4A CN201610412887A CN107488161A CN 107488161 A CN107488161 A CN 107488161A CN 201610412887 A CN201610412887 A CN 201610412887A CN 107488161 A CN107488161 A CN 107488161A
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- CN
- China
- Prior art keywords
- olopatadine
- butyl
- light method
- transformation according
- light
- 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.)
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D313/12—[b,e]-condensed
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
With more E-isomer in olopatadine synthesis, the invention discloses a kind of smooth method for transformation, olopatadine N-butyl is in appropriate solvent, in the presence of certain carrier, through light irradiation appropriate time, E-isomer can be changed into Z-type, the latter obtains final products by hydrolysis.The present invention has easy to operate, and raw material is easy to get, and the features such as high conversion rate, greatly improves the yield of olopatadine.
Description
Technical field
The present invention relates to a kind of method of olopatadine N-butyl isomers light conversion, belongs to chemical synthesis and technique neck
Domain.
Background technology
Olopatadine hydrochloride is by the research and development of consonance fermentation company of Japan.Japanese Ai Erkang (Alcon) companies draw from consonance company
Enter and developed into 0.1% eye drops.Olopatadine is mast cell stabilizers and relative selectivity histamine H 1- receptor antagonists
Agent.I type type Ⅰ hypersensitivity reactions can be suppressed in live body and experiment in vitro.Olopatadine is to alpha-adrenergic receptor, DOPA
Amine receptor, muscarine I types and II receptors and 5-hydroxytryptamine receptor do not act on.Available for treatment allergic asthma and anaphylaxis
Itch caused by conjunctivitis.In olopatadine synthesis, more isomers generation is frequently accompanied by, this is to follow-up refined or yield
All adversely affect, the present invention, which discloses one kind, can make intermediate product E-isomer be converted into Z-type intermediate, and the latter is through hydrolysis
Obtain olopatadine.The present invention have it is simple to operate, the high feature of raw material availability, be easy to industrial production.
The content of the invention
The technical problems to be solved by the invention are to provide a kind of method of olopatadine N-butyl isomers light conversion,
In order to solve the above technical problems, the technical solution adopted by the present invention is as follows：
。
（1）Compound 8, by ultraviolet light, prepares chemical combination in silica-gel carrier, dichloromethane and methanol mixed solvent
Thing 9, a diameter of 200-300 mesh of silica gel, a length of 350nm-400nm of ultraviolet light wave, dichloromethane：Methanol is 80：1—20：1,
Irradiation time is 20-80 hours.
Step（1）Described olopatadine N-butyl light method for transformation, it is characterised in that silica-gel carrier particle diameter is
100-200 mesh, 200-300 mesh.It is preferred that 100-200 mesh, most preferably 200-300 mesh.
Step（1）Described olopatadine N-butyl light method for transformation, it is characterised in that ultraviolet light wave a length of 300-
350nm, 350-400nm.It is preferred that 300-350nm, most preferably 350-400nm.
Step（1）Described olopatadine N-butyl light method for transformation, it is characterised in that selected mixed solvent, two
Chloromethanes：Methanol is 100：1—10：Between 1, preferably 80：1, most preferably 20：1.
Step（1）Described olopatadine N-butyl light method for transformation, it is characterised in that irradiation time is 4-100 small
When, preferably 10-80 hours, most preferably 10-40 hours.
The invention has the advantages that：Operation is convenient, and raw material is cheap and easy to get, high income.
Embodiment
According to following embodiments, the present invention may be better understood.It is however, as it will be easily appreciated by one skilled in the art that real
Apply the content described by example and be merely to illustrate the present invention, without should be also without limitation on sheet described in detail in claims
Invention.
Embodiment 1：
2g is taken to contain the olopatadine N-butyl mixture of E types and Z-type（The Z-type 4.0% of E types 95.9%）, it is dissolved in 20ml bis-
Chloromethanes：Methanol=20：In 1 mixed liquor, the mesh silica gel of 20g 200-300 is added, is loaded on after mixing thoroughly in test tube, it is purple in 350nm
Filtering and concentrating after irradiation 35 is small under outer lamp, is able to the product mix based on Z-type olopatadine N-butyl（The Z-type of E types 10.1%
87.4%）.
Embodiment 2：
2g is taken to contain the olopatadine N-butyl mixture of E types and Z-type（The Z-type 64.2% of E types 31.0%）, it is dissolved in 20ml bis-
Chloromethanes：Methanol=15：In 1 mixed liquor, the mesh silica gel of 20g 200-300 is added, is loaded on after mixing thoroughly in test tube, it is purple in 380nm
Filtering and concentrating after irradiation 20 is small under outer lamp, is able to the product mix based on Z-type olopatadine N-butyl（The Z-type of E types 5.5%
88.0%）.
Embodiment 3：
20g is taken to contain the olopatadine N-butyl mixture of E types and Z-type（The Z-type 55.2% of E types 41.5%）, it is dissolved in 20ml bis-
Chloromethanes：Methanol=10：In 1 mixed liquor, the mesh silica gel of 50g 200-300 is added, it is purple in 400nm after mixing thoroughly in dress and test tube
Filtering and concentrating after irradiation 40 is small under outer lamp, is able to the product mix based on Z-type olopatadine N-butyl（The Z-type of E types 7.1%
88.9%）.
The technical concepts and features of embodiment described above only to illustrate the invention, it can not limit the present invention's with this
Protection domain.The equivalent change or modification that all design key according to the present invention are done, should all cover the protection model in the present invention
Within enclosing.
Claims (8)
1. a kind of synthetic route of olopatadine is as follows, wherein compound 5 and compound 7 can be generated each other along anteiso- by reaction
The compound 8 and 9 of structure, for compound 8 in the presence of certain carrier, light is converted into compound 9：
2. olopatadine N-butyl light method for transformation according to claim 1, it is characterised in that carrier used is silica gel,
Macroreticular resin, most preferably preferred resin, silica gel.
3. olopatadine N-butyl light method for transformation according to claim 1, it is characterised in that optical wavelength used in light conversion
For visible ray, most preferably ultraviolet light, preferably visible ray, ultraviolet light.
4. olopatadine N-butyl light method for transformation according to claim 1, it is characterised in that solvent can be methanol, two
Chloromethanes, most preferably ethyl acetate, preferably dichloromethane, methanol and dichloromethane mixture.
5. olopatadine N-butyl light method for transformation according to claim 1, it is characterised in that silica-gel carrier particle diameter
For 100-200 mesh, 200-300 mesh；It is preferred that 100-200 mesh, most preferably 200-300 mesh.
6. the olopatadine N-butyl light method for transformation according to patent requirements 1, it is characterised in that ultraviolet light wave a length of 300-
350nm, 350-400nm；It is preferred that 300-350nm, most preferably 350-400nm.
7. olopatadine N-butyl light method for transformation according to claim 1, it is characterised in that selected mixing is molten
Agent, dichloromethane：Methanol is 100：1—10：Between 1, preferably 80：1, most preferably 20：1.
8. olopatadine N-butyl light method for transformation according to claim 1, it is characterised in that irradiation time is 4-100
Hour, preferably 10-80 hours, most preferably 10-40 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610412887.4A CN107488161A (en) | 2016-06-13 | 2016-06-13 | A kind of light method for transformation of olopatadine N-butyl isomers |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610412887.4A CN107488161A (en) | 2016-06-13 | 2016-06-13 | A kind of light method for transformation of olopatadine N-butyl isomers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107488161A true CN107488161A (en) | 2017-12-19 |
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ID=60642138
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610412887.4A Pending CN107488161A (en) | 2016-06-13 | 2016-06-13 | A kind of light method for transformation of olopatadine N-butyl isomers |
Country Status (1)
| Country | Link |
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| CN (1) | CN107488161A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007110761A2 (en) * | 2006-03-28 | 2007-10-04 | Universität Zürich | Polymorphic forms of olopatadine hydrochloride and methods for producing olopatadine and salts thereof |
| CN101815709A (en) * | 2007-10-05 | 2010-08-25 | 住友化学株式会社 | Method for producing dibenzoxepin compound |
-
2016
- 2016-06-13 CN CN201610412887.4A patent/CN107488161A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007110761A2 (en) * | 2006-03-28 | 2007-10-04 | Universität Zürich | Polymorphic forms of olopatadine hydrochloride and methods for producing olopatadine and salts thereof |
| CN101815709A (en) * | 2007-10-05 | 2010-08-25 | 住友化学株式会社 | Method for producing dibenzoxepin compound |
Non-Patent Citations (1)
| Title |
|---|
| 刘敏: "盐酸奥洛他定的合成", 《合成化学》 * |
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Application publication date: 20171219 |