AU2016102260A4 - Methimidol pharmaceutical intermediate 1- (β- hydroxyethyl) -2-methylimidazole synthesis method - Google Patents
Methimidol pharmaceutical intermediate 1- (β- hydroxyethyl) -2-methylimidazole synthesis method Download PDFInfo
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- AU2016102260A4 AU2016102260A4 AU2016102260A AU2016102260A AU2016102260A4 AU 2016102260 A4 AU2016102260 A4 AU 2016102260A4 AU 2016102260 A AU2016102260 A AU 2016102260A AU 2016102260 A AU2016102260 A AU 2016102260A AU 2016102260 A4 AU2016102260 A4 AU 2016102260A4
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Abstract
Methimidol pharmaceutical intermediate 1- (0- hydroxyethyl) -2-methylimidazole synthesis method , comprising the following steps: (i) equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 1.3mol 2-methylimidazole (2), 1.5-1.7mol amine alcohols, 200ml nitroethane, raised the solution temperature to 70 - 75 C, reflux for 9-10 h, reducing the temperature of the solution to 50--55 C, standing layered and got out lower liquid, dissolved in 1.3-1.6L propionitrile solution, reducing the solution temperature to 13 - 15 C, added 130ml oxalic acid solution, reducing the solution temperature to 2--4 C, suction filtered, washed with 130ml cyclohexane solution, and recrystallized from acetonitrile solution, decolorized with molecular sieve, controlling the stirring rate 90-110rpm, after 2-3h , the precipitated solid was washed with salt solution, washed with isopropanol solution, dehydrated with dehydrating agent, drying at 70 - 75 C, got 1- ( hydroxyethyl) -2-methylimidazole.
Description
Methimidol pharmaceutical intermediate 1- (β- hydroxyethyl) -2-methylimidazole synthesis method
TECHNICAL FIELD
The present invention relates to methimidol pharmaceutical intermediate 1- (β- hydroxyethyl) -2-methylimidazole synthesis method.
BACKGROUND ART
Methimidol drugs is acting on the circulatory system as a vasoactive drugs belong to adrenergic drugs, pharmacologically active contraction of blood vessels, topical application, relieve nasal swelling and congestion. It has a direct effect on α-adrenergic agents markedly enable intranasal expansion small arteries, but no - receptor on β-adrenergic. After topical application, action can occur within 10 minutes, continued for 2 to 6 hours. Clinically it is for the treatment of acute and chronic nasal various causes, eyes, pharyngeal mucosa congestion, such as allergies, inflammation, infections and other pathogenic microorganisms, and alleviate the eyelid muscle spasm. 1- (β-hydroxyethyl) -2-methylimidazole as methimidol drug intermediates, its synthesis method is of great economic significance for improving drug synthesis product quality, reducing the by-product content.
SUMMARY OF THE INVENTION
Object of the present invention is to provide methimidol pharmaceutical intermediate 1- (β- hydroxyethyl) -2-methylimidazole synthesis method , comprising the following steps: (i) equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 1.3mol 2-methylimidazole (2), 1.5-1.7mol amine alcohols, 200ml nitroethane, raised the solution temperature to 70 - 75 °C, reflux for 9-10 h, reducing the temperature of the solution to 50—55 °C, standing layered and got out lower liquid, dissolved in 1.3-1.6L propionitrile solution, reducing the solution temperature to 13 - 15 °C, added 130ml oxalic acid solution, reducing the solution temperature to 2—4 °C, suction filtered, washed with 130ml cyclohexane solution, and recrystallized from acetonitrile solution, decolorized with molecular sieve, controlling the stirring rate 90-110rpm, after 2-3h , the precipitated solid was washed with salt solution, washed with isopropanol solution, dehydrated with dehydrating agent, drying at 70 - 75 °C, got 1- (β-hydroxyethyl) -2-methylimidazole (1); wherein propionitrile solution in step (i) has a mass fraction of 80-85%; oxalic acid solution in step (i) has a mass fraction of 30-35%, cyclohexane solution in step (i) has a mass fraction of 70-75%, acetonitrile solution in step (i) has a mass fraction of 85-90%, salt solution in step (i) is any one of potassium bromide solution or sodium sulfate solution; isopropanol solution in step (i) has a mass fraction of 85-90%, dehydrating agent in step (i) is any one of anhydrous calcium sulfate or anhydrous potassium carbonate.
The throughout reaction process can be summarized using the following reaction formula:
Advantage of the present invention is that: the reaction intermediate links are reduced, reducing the reaction temperature and reaction time, improving the reaction yield.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION
Embodiment 1
Equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 1.3mol 2-methylimidazole (2), 1.5 mol amine alcohols, 200ml nitroethane, raised the solution temperature to 70 °C, reflux for 9 h, reducing the temperature of the solution to 50 °C, standing layered and got out lower liquid, dissolved in 1.3 L propionitrile solution with a mass fraction of 80% , reducing the solution temperature to 13°C, added 130ml oxalic acid solution with a mass fraction of 30%, reducing the solution temperature to 2 °C, suction filtered, washed with 130ml cyclohexane solution with a mass fraction of 70%, and recrystallized from acetonitrile solution with a mass fraction of 85%, decolorized with molecular sieve, controlling the stirring rate 90-110rpm, after 2-3h , the precipitated solid was washed with potassium bromide solution , washed with isopropanol solution with a mass fraction of 85%, dehydrated with anhydrous calcium sulfate dehydrating agent, drying at 70 °C, got 1- (β-hydroxyethyl) -2-methylimidazole 85.18 g, yield 52%.
Embodiment 2
Equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 1.3mol 2-methylimidazole (2), 1.7 mol amine alcohols, 200ml nitroethane, raised the solution temperature to 75 °C, reflux for 10 h, reducing the temperature of the solution to 55 °C, standing layered and got out lower liquid, dissolved in 1.6 L propionitrile solution with a mass fraction of 85% , reducing the solution temperature to 15°C, added 130ml oxalic acid solution with a mass fraction of 35%, reducing the solution temperature to 4 °C, suction filtered, washed with 130ml cyclohexane solution with a mass fraction of 75%, and recrystallized from acetonitrile solution with a mass fraction of 90%, decolorized with molecular sieve, controlling the stirring rate 90-110rpm, after 2-3h , the precipitated solid was washed with potassium bromide solution , washed with isopropanol solution with a mass fraction of 90%, dehydrated with anhydrous potassium carbonate dehydrating agent, drying at 70 °C, got 1- (β- hydroxyethyl) -2-methylimidazole 96.64 g, yield 59%.
Embodiment 3
Equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 1.3mol 2-methylimidazole (2), 1.7 mol amine alcohols, 200ml nitroethane, raised the solution temperature to 75 °C, reflux for 10 h, reducing the temperature of the solution to 55 °C, standing layered and got out lower liquid, dissolved in 1.6 L propionitrile solution with a mass fraction of 85% , reducing the solution temperature to 15°C, added 130ml oxalic acid solution with a mass fraction of 35%, reducing the solution temperature to 4 °C, suction filtered, washed with 130ml cyclohexane solution with a mass fraction of 75%, and recrystallized from acetonitrile solution with a mass fraction of 90%, decolorized with molecular sieve, controlling the stirring rate 90-110rpm, after 2-3h , the precipitated solid was washed with potassium bromide solution , washed with isopropanol solution with a mass fraction of 90%, dehydrated with anhydrous calcium sulfate dehydrating agent, drying at 75 °C, got 1- (β- hydroxyethyl) -2-methylimidazole 126.12 g, yield 63%.
While a number of preferred embodiments have been described, it will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.
Claims (4)
1. Methimidol pharmaceutical intermediate 1- (β- hydroxyethyl) -2-methylimidazole synthesis method , comprising the following steps: (i) equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 1.3mol 2-methylimidazole (2), 1.5-1.7mol amine alcohols, 200ml nitroethane, raised the solution temperature to 70 - 75 °C, reflux for 9-10 h, reducing the temperature of the solution to 50—55 °C, standing layered and got out lower liquid, dissolved in 1.3-1.6L propionitrile solution, reducing the solution temperature to 13 - 15 °C, added 130ml oxalic acid solution, reducing the solution temperature to 2—4 °C, suction filtered, washed with 130ml cyclohexane solution, and recrystallized from acetonitrile solution, decolorized with molecular sieve, controlling the stirring rate 90-110rpm, after 2-3h , the precipitated solid was washed with salt solution, washed with isopropanol solution, dehydrated with dehydrating agent, drying at 70 - 75 °C, got 1- (β-hydroxyethyl) -2-methylimidazole (1); wherein propionitrile solution in step (i) has a mass fraction of 80-85%; oxalic acid solution in step (i) has a mass fraction of 30-35%, cyclohexane solution in step (i) has a mass fraction of 70-75%, acetonitrile solution in step (i) has a mass fraction of 85-90%.
2. Methimidol pharmaceutical intermediate 1- (β- hydroxyethyl) -2-methylimidazole synthesis method according to claim 1 wherein salt solution in step (i) is any one of potassium bromide solution or sodium sulfate solution.
3. Methimidol pharmaceutical intermediate 1- (β- hydroxyethyl) -2-methylimidazole synthesis method according to claim 1 wherein isopropanol solution in step (i) has a mass fraction of 85-90%.
4. Methimidol pharmaceutical intermediate 1- (β- hydroxyethyl) -2-methylimidazole synthesis method according to claim 1 wherein dehydrating agent in step (i) is any one of anhydrous calcium sulfate or anhydrous potassium carbonate.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510991262.3A CN105461631A (en) | 2015-12-24 | 2015-12-24 | Synthetic method of methimidol hydrochloride medicine intermediate 1-(beta-hydroxyethyl)-2-methylimidazole |
| CN2015109912623 | 2015-12-24 | ||
| CN201610817282.3A CN106432088A (en) | 2015-12-24 | 2016-09-12 | Method for synthesizing methimidol hydrochloride medicine intermediate 1-(beta-ethoxy)-2-methylimidazole |
| CN2016108172823 | 2016-09-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2016102260A4 true AU2016102260A4 (en) | 2017-02-23 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2016102260A Ceased AU2016102260A4 (en) | 2015-12-24 | 2016-12-23 | Methimidol pharmaceutical intermediate 1- (β- hydroxyethyl) -2-methylimidazole synthesis method |
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| Country | Link |
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| AU (1) | AU2016102260A4 (en) |
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2016
- 2016-12-23 AU AU2016102260A patent/AU2016102260A4/en not_active Ceased
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