CN101037401B - High-purity methoxyamine methane sulfonic acid salt and preparation method thereof - Google Patents
High-purity methoxyamine methane sulfonic acid salt and preparation method thereof Download PDFInfo
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- CN101037401B CN101037401B CN2006100433107A CN200610043310A CN101037401B CN 101037401 B CN101037401 B CN 101037401B CN 2006100433107 A CN2006100433107 A CN 2006100433107A CN 200610043310 A CN200610043310 A CN 200610043310A CN 101037401 B CN101037401 B CN 101037401B
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Abstract
The invention discloses a methoxy ammonium methanesulfonate and its producing method which is characterized in that including the steps of: reacting with a methoxylamine and methanesulfonic acid, getting a methoxy ammonium methanesulfonate with a high purity after dehydration, recrystallization, centrifugation and drying, which is white, has a melting point range of 99-101.5 DEG C, moisture of 0.1-0.5 %, gas phase chromatography of 99-9905%. The product is a medical intermediate with a chemical purity up to 99% and a good stability, which can make the reaction smoothly in a special condition.
Description
Technical field:
The present invention relates to the medicine intermediate technical field, is a kind of high-purity methoxyamine methane sulfonic acid salt and preparation method thereof specifically.
Background technology:
At present, Vasoxyl is usually used in the reactions such as introducing of oxime as a kind of important drugs midbody, but Vasoxyl is extremely unstable, can stable existence after the acidifying with the form of salt, and generally be that form with hydrochloride exists and in reaction, uses.But in some special reaction occasions, can have a strong impact on the carrying out of reaction under the condition like the existence of cl ions, thereby the application of the hydrochloride that generates as souring agent and the reaction of methoxyl group amine with hydrochloric acid receives certain limitation.
Summary of the invention;
The objective of the invention is to overcome the deficiency of above-mentioned prior art, and a kind of high-purity methoxyamine methane sulfonic acid salt is provided.
Another object of the present invention provides a kind of high-purity methoxyamine methane sulfonic acid salt and preparation method thereof.
The application that the present invention has mainly solved the existing hydrochloric acid hydrochloride that reaction generates as souring agent and methoxyl group amine receives certain limitation, under some special reaction conditions, and the problem that reaction is had a strong impact on.
In order to achieve the above object, the present invention is achieved in that high-purity methoxyamine methane sulfonic acid salt, it is characterized in that it is to be carried out to reactant salt by Vasoxyl and methylsulphonic acid; Make high-purity methoxyamine methane sulfonic acid salt through dehydration, recrystallization, centrifugal, drying course; Its outward appearance is a white crystal, melting range 99-101.5 ℃, and moisture 0.1-0.5%; Gc 99-99.5%, chemistry titration 99-99.5%.
The preparation method of high-purity methoxyamine methane sulfonic acid salt of the present invention, it comprises following process step:
A, salify drips methylsulphonic acid in Vasoxyl, drip to PH >=2.0, and temperature is 0-40 ℃;
B, the material behind the salify is heated in dehydration, and heating and temperature control is 60-110 ℃, dewaters, and during anhydrous steaming, stops heating and the processing of lowering the temperature in the material to salify;
C, recrystallization when the material after the dehydration is cooled to 0-40 ℃, adds absolute ethyl alcohol, and begins heating, after dissolving entirely to material, stops heating, and lowers the temperature, and < T≤15 ℃ stop cooling being cooled to 0 ℃;
D, centrifugal and oven dry adopts whizzer to dry, and the solid matter after the drying drenches with the room temperature absolute ethyl alcohol, after drying once more, dries, and bake out temperature is controlled to be 25-95 ℃, gets high-purity methoxyamine methane sulfonic acid salt after the oven dry.
Compared with present technology high-purity methoxyamine methane sulfonic acid salt of the present invention and preparation method thereof has outstanding substantive distinguishing features and obvious improvement; Because the unreactiveness that has of methylsulphonic acid itself can satisfy the unreactiveness of reaction process needs such as oximate; Material after Vasoxyl and the methylsulphonic acid salt-forming reaction can stable existence; In the special reaction occasion, reaction is carried out smoothly simultaneously, its chemical purity can reach 99%.
Embodiment:
In order to understand better and to implement, specify high-purity methoxyamine methane sulfonic acid salt of the present invention and preparation method thereof below in conjunction with embodiment.
Embodiment 1, in reactor, adds methoxamine, begins to stir, and logical cooling water in the chuck of reactor when temperature of charge is reduced to 40 ℃ in the still, slowly drips pyrovinic acid in still, and holding temperature is 40 ℃, to PH be 2.0; Under continuous stirring; Stop logical cooling water in the chuck of reactor; Be converted to logical steam; Material in reactor is dewatered; It is 110 ℃ that the steam regulation valve is controlled reactor temperature; Note the variation of material in the still therebetween, stop logical steam during substantially anhydrous steaming in the still, and switch to cooling water material in the still is lowered the temperature; When material in the still cools to 40 ℃; Add absolute ethyl alcohol; This moment, the chuck of reactor stopped logical cooling water; Switch to logical steam to material heating in the still; After material in the still dissolves entirely, stop heating, the chuck of reactor switches to logical chilled brine by logical steam material in the still is lowered the temperature; When material in the still is cooled to 15 ℃, stop cooling; Material in the reactor is put into centrifuge dry, the solids after the drying drenches with the room temperature absolute ethyl alcohol, and the solids after drying is once more packed in the baker, and bake out temperature is 95 ℃, after the oven dry high-purity methoxyamine methane sulfonic acid salt.Its outward appearance is a white crystal, and recording its melting range is 99.2-101.1 ℃, moisture 0.42%, gc 99.01%, chemistry titration 99.02%.
Embodiment 2, in reactor, add methoxamine, begin to stir, and logical cooling water in the chuck of reactor when temperature of charge is reduced to 0 ℃ in the still, slowly drips pyrovinic acid in still, and holding temperature is 0 ℃, to PH be 5; Under continuous stirring; Stop logical cooling water in the chuck of reactor; Be converted to logical steam; Material in reactor is dewatered; It is 100 ℃ that the steam regulation valve is controlled reactor temperature; Note the variation of material in the still therebetween, stop logical steam during substantially anhydrous steaming in the still, and switch to cooling water material in the still is lowered the temperature; When material in the still cools to 0 ℃; Add absolute ethyl alcohol; This moment, the chuck of reactor stopped logical cooling water; Switch to logical steam to material heating in the still; After material in the still dissolves entirely, stop heating, the chuck of reactor switches to logical chilled brine by logical steam material in the still is lowered the temperature; When material in the still is cooled to 0 ℃, stop cooling; Material in the reactor is put into centrifuge dry, the solids after the drying drenches with the room temperature absolute ethyl alcohol, and the solids after drying is once more packed in the vacuum drying device, and bake out temperature is 25 ℃, after the oven dry high-purity methoxyamine methane sulfonic acid salt.
Embodiment 3, in reactor, add methoxamine, begin to stir, and logical cooling water in the chuck of reactor when temperature of charge is reduced to 20 ℃ in the still, slowly drips pyrovinic acid in still, and holding temperature is 20 ℃, to PH be 8.0; Under continuous stirring; Stop logical cooling water in the chuck of reactor; Be converted to logical steam; Material in reactor is carried out vacuum dehydration; It is 60 ℃ that the steam regulation valve is controlled reactor temperature; Note the variation of material in the still therebetween, stop logical steam during substantially anhydrous steaming in the still, and switch to cooling water material in the still is lowered the temperature; When material in the still cools to 20 ℃; Add absolute ethyl alcohol; This moment, the chuck of reactor stopped logical cooling water; Switch to logical steam to material heating in the still; After material in the still dissolves entirely, stop heating, the chuck of reactor switches to logical chilled brine by logical steam material in the still is lowered the temperature; When material in the still is cooled to 10 ℃, stop cooling; Material in the reactor is put into centrifuge dry, the solids after the drying drenches with the room temperature absolute ethyl alcohol, and the solids after drying is once more packed in the vacuum drying device, and bake out temperature is 60 ℃, after the oven dry high-purity methoxyamine methane sulfonic acid salt.
Claims (2)
1. high-purity methoxyamine methane sulfonic acid salt; It is characterized in that it is to be carried out to reactant salt by Vasoxyl and methylsulphonic acid, make high-purity methoxyamine methane sulfonic acid salt through dehydration, recrystallization, centrifugal, drying course, its outward appearance is a white crystal; Melting range 99-101.5 ℃; Moisture 0.1-0.5%, gc 99-99.5%, chemistry titration 99-99.5%.
2. the preparation method of the described high-purity methoxyamine methane sulfonic acid salt of claim 1, it comprises following process step:
A, salify drips methylsulphonic acid in Vasoxyl, drip to pH >=2.0, and temperature is 0-40 ℃;
B, the material behind the salify is heated in dehydration, and heating and temperature control is 60-110 ℃, dewaters, and during anhydrous steaming, stops heating and the processing of lowering the temperature in the material to salify;
C, recrystallization when the material after the dehydration is cooled to 0-40 ℃, adds absolute ethyl alcohol, and begins heating, after dissolving entirely to material, stops heating, and lowers the temperature, and is cooled to 0 ℃＜T≤15 ℃, stops cooling;
D, centrifugal and oven dry adopts whizzer to dry, and the solid matter after the drying drenches with the room temperature absolute ethyl alcohol, after drying once more, dries, and bake out temperature is controlled to be 25-95 ℃, gets high-purity methoxyamine methane sulfonic acid salt after the oven dry.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2006100433107A CN101037401B (en) | 2006-03-17 | 2006-03-17 | High-purity methoxyamine methane sulfonic acid salt and preparation method thereof |
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| CN2006100433107A CN101037401B (en) | 2006-03-17 | 2006-03-17 | High-purity methoxyamine methane sulfonic acid salt and preparation method thereof |
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| CN101037401B true CN101037401B (en) | 2012-01-25 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5382685A (en) * | 1992-10-05 | 1995-01-17 | Basf Aktiengesellschaft | Preparation of O-substituted hydroxylammonium salts |
| US5488162A (en) * | 1994-01-03 | 1996-01-30 | Buckland; Paul R. | Process for preparing o-alkylhydroxylamine salts without the isolation of intermediates |
| US5777164A (en) * | 1997-04-14 | 1998-07-07 | Eastman Chemical Company | Process for the preparation of high purity O-substituted hydroxylamine derivatives |
-
2006
- 2006-03-17 CN CN2006100433107A patent/CN101037401B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5382685A (en) * | 1992-10-05 | 1995-01-17 | Basf Aktiengesellschaft | Preparation of O-substituted hydroxylammonium salts |
| US5488162A (en) * | 1994-01-03 | 1996-01-30 | Buckland; Paul R. | Process for preparing o-alkylhydroxylamine salts without the isolation of intermediates |
| US5777164A (en) * | 1997-04-14 | 1998-07-07 | Eastman Chemical Company | Process for the preparation of high purity O-substituted hydroxylamine derivatives |
Non-Patent Citations (1)
| Title |
|---|
| 季永新.甲氧胺盐酸盐的合成.《化学与粘合》.2001,(第5期),200-202. * |
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