CN106432221B - A kind of process for purification of Homatropine Methylbromide - Google Patents
A kind of process for purification of Homatropine Methylbromide Download PDFInfo
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- CN106432221B CN106432221B CN201610833383.XA CN201610833383A CN106432221B CN 106432221 B CN106432221 B CN 106432221B CN 201610833383 A CN201610833383 A CN 201610833383A CN 106432221 B CN106432221 B CN 106432221B
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- Prior art keywords
- organic solvent
- homatropine methylbromide
- purification
- homatropine
- methylbromide
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
- C07D451/10—Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
Abstract
A kind of process for purification of Homatropine Methylbromide, is mainly included the following steps that：Homatropine Methylbromide is dissolved in a kind of organic solvent A and heated, is then added in another organic solvent B, crystallisation by cooling.Method provided by the invention can make the purity of Homatropine Methylbromide meet CP USP EP standards, reaction condition is gentle, easy to operate, is suitable for industrialized production up to more than 99.5%.
Description
Technical field
Field of medicaments of the present invention, and in particular to the process for purification of Homatropine Methylbromide.
Background technology
At present, Homatropine Methylbromide, also known as homapin, English name Homatropine Methylbromide.
It is that there is blockage of acetylcholine, makes sphincter pupillae and cycloplegia and cause mydriasis and paralysis accommodation.It is blocked
The ability of cholinergic nerve, it is faster and weak than atropine.The duration of its mydriasis and paralysis accommodation effect is short far beyond atropine, and
Adverse reaction is slight, and unrestraint secretion makes larynx feel dry side effect.It thus be accordingly used in mydriasis and check that eyeground and optometry are compared
It is convenient.On the document of Homatropine Methylbromide preparation method and few, pertinent literature has：“research and industry,
1972,17 (3), the technique that 92-93 " is reacted by tropanol and O- acetylmandeloyls chlorine prepare homatropinum;Patent
SU199149 and DD11056 prepares homatropinum by tropanol and the direct reaction of mandelic acid;Also domestic patent CN
101643473A prepares homatropinum by tropanol and O- formoxyl almond acyl chloride reactions, then prepares horse support after hydrobromic acid
Product.It is not involved with the document and patent of Homatropine Methylbromide process for purification.
The content of the invention
The purpose of the present invention provides a kind of first bromine aiming at the deficiency currently without Homatropine Methylbromide process for purification
Homatropinum process for purification.
Specific purification step of the invention is as follows:
Homatropine Methylbromide crude product is placed in organic solvent A, is heated to 50-90 DEG C of dissolvings, continues to stir 15-
25min, then the solution after above-mentioned dissolving is gradually added into organic solvent B and stirred, then cooling down to-20-20 DEG C are tied
Crystalline substance, growing the grain 2 hours, filter, 60 DEG C of vacuum dryings 5 hours, obtain Homatropine Methylbromide fine work.
Organic solvent A is the mixture of one kind or more than at least two in methanol, ethanol, propyl alcohol and/or isopropanol.
Organic solvent B is the mixing of one kind or more than at least two in acetone, isopropanol, ethyl acetate and/or MTBE
Thing.
Horse tropine crude product is 1 with organic solvent A product quality ratio：0.5-5.
Organic solvent A is 1 with organic solvent B product quality ratio：3-15.
The method have the advantages that：This method is mainly for the refined of Homatropine Methylbromide crude product, and reaction condition is gentle, operation letter
Just, it is suitable for industrialized production.
Embodiment
The present invention comprises the following steps that:
Homatropine Methylbromide crude product is placed in organic solvent A, is heated to 50-90 DEG C of dissolvings（50- is warming up in 60min
90℃）, preferably 60-80 DEG C, continue to stir 15-25min, preferably 20 min, it is at room temperature, the solution after above-mentioned dissolving is gradual
Add in organic solvent B and stir, then cooling down to-20-20 DEG C crystallize, and preferably-5-5 DEG C crystallizations, growing the grain 2 hours, take out
Filter, 60 DEG C of vacuum dryings 5 hours, obtains Homatropine Methylbromide fine work.
Organic solvent A is the mixture of one kind or more than at least two in methanol, ethanol, propyl alcohol and/or isopropanol.
Organic solvent B is the mixing of one kind or more than at least two in acetone, isopropanol, ethyl acetate and/or MTBE
Thing.
Homatropine Methylbromide crude product is 1 with organic solvent A product quality ratio：0.5-5, preferably 1：1-2.
Organic solvent A is 1 with organic solvent B product quality ratio：3-15, preferably 1：5-8.
Embodiment 1
Take Homatropine Methylbromide crude product 100g（Purity 98.2%）, add in 150g ethanol, be warming up to 75 DEG C of dissolvings, continue
20min or so is stirred, at room temperature, above-mentioned solution is added gradually to stir in 1000g acetone, then cooling down to 0 DEG C of left side
Right crystallization, growing the grain 2 hours.Filter, 60 DEG C of vacuum dryings 7 hours, obtain Homatropine Methylbromide fine work 75.6g.
Embodiment 2
Take Homatropine Methylbromide crude product 100g（Purity 98.2%）, add in 100g methanol, be warming up to 60 DEG C of dissolvings, continue
20min or so is stirred, at room temperature, above-mentioned solution is added gradually to stir in 800g acetone, then cooling down is to 0 DEG C or so
Crystallization, growing the grain 2 hours.Filter, 60 DEG C of vacuum dryings 5 hours, obtain Homatropine Methylbromide fine work 72.3g.
Claims (1)
- A kind of 1. process for purification of Homatropine Methylbromide, it is characterised in that:Comprise the following steps that:Homatropine Methylbromide crude product will be contained It is placed in organic solvent A, is heated to 50-90 DEG C of dissolvings, continues to stir 15-25min, then the solution after above-mentioned dissolving is cooled down To normal temperature, it is gradually added into organic solvent B and stirs, then cooling down to-20-20 DEG C crystallizes, growing the grain 2 hours, filter, 60 DEG C vacuum drying 5 hours, obtains Homatropine Methylbromide fine work；The organic solvent A is in methanol, ethanol, propyl alcohol and/or isopropanol One kind or more than at least two mixture；The organic solvent B is in acetone, isopropanol, ethyl acetate and/or MTBE It is a kind of or more than at least two mixture；Homatropine Methylbromide crude product and the mass ratio of organic solvent A are 1:0.5-5；It is organic Solvent orange 2 A and the mass ratio of organic solvent B are 1:3-15.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610833383.XA CN106432221B (en) | 2016-09-20 | 2016-09-20 | A kind of process for purification of Homatropine Methylbromide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610833383.XA CN106432221B (en) | 2016-09-20 | 2016-09-20 | A kind of process for purification of Homatropine Methylbromide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106432221A CN106432221A (en) | 2017-02-22 |
| CN106432221B true CN106432221B (en) | 2018-01-12 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610833383.XA Active CN106432221B (en) | 2016-09-20 | 2016-09-20 | A kind of process for purification of Homatropine Methylbromide |
Country Status (1)
| Country | Link |
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| CN (1) | CN106432221B (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101643473B (en) * | 2009-08-28 | 2011-11-09 | 浙江工业大学 | Synthesis method of homatropine hydrobromide |
-
2016
- 2016-09-20 CN CN201610833383.XA patent/CN106432221B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| Combined Use of Ionic Liquid and Hydroxypropyl-b-Cyclodextrin for the Enantioseparation of Ten Drugs by Capillary Electrophoresis;YAN CUI等;《CHIRALITY》;20130606;第25卷(第7期);409-414 * |
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| CN106432221A (en) | 2017-02-22 |
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Address after: No.122, Yangwan Road, Duodao District, Jingmen high tech Zone, Hubei Province Patentee after: Hubei Hendi Pharmaceutical Co., Ltd Address before: Jingmen City, Hubei Province, Yang Wan Lu 448124 Duodao District No. 122 Patentee before: HUBEI BAIKEHENGDI PHARMACEUTICAL Co.,Ltd. |
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