AU2016102309A4 - Furtrethonium iodide pharmaceutical intermediate 2- dimethylamino-methylfuran synthesis method - Google Patents
Furtrethonium iodide pharmaceutical intermediate 2- dimethylamino-methylfuran synthesis method Download PDFInfo
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- AU2016102309A4 AU2016102309A4 AU2016102309A AU2016102309A AU2016102309A4 AU 2016102309 A4 AU2016102309 A4 AU 2016102309A4 AU 2016102309 A AU2016102309 A AU 2016102309A AU 2016102309 A AU2016102309 A AU 2016102309A AU 2016102309 A4 AU2016102309 A4 AU 2016102309A4
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Abstract
Furtrethonium iodide pharmaceutical intermediate 2 dimethylamino-methylfuran synthesis method, comprising the following steps: equipped with a stirrer, a thermometer and a dropping funnel , the reaction vessel was added 1.6mol dimethylamine methanol solution (3), 500ml oxalic acid solution, 1.8 mol alumina, 2.1-2.6mol 2-furan dimethanol solution (2), controlling the stirring speed 130-170rpm, raised the solution temperature to 120-128 0C, continued the reaction for 5-8h, reducing the temperature of the solution to 90--96 0C, refluxed for 2-3h, added 130ml phosphoric acid solution after cooling, increased solution temperature to 60--66 0C, stirred for 90-130 min, added 300ml sodium sulfite solution, continued reaction for 80-110min, the temperature of the solution is reduced to 10 - 15 0C, added 1 10ml potassium hydrogen sulfite solution, allowed to stand for 3-5h, the solution appeared layer, separated the oil, the aqueous layer was extracted for 5-8 times with nitromethane solution, combined oil layer, dehydrated with dehydration agent, vacuum distillation, collecting fractions of 110--116 0C, recrystallized from toluene solution, got 2- dimethylamino-methylfuran .
Description
Furtrethonium iodide pharmaceutical intermediate 2-dimethylamino-methylfuran synthesis method
TECHNICAL FIELD
The present invention relates to furtrethonium iodide pharmaceutical intermediate 2- dimethylamino-methylfuran synthesis method.
BACKGROUND ART
Furtrethonium iodide is primary used for glaucoma medications, including open-angle and angle-closure glaucoma. After instillation, miotic effect appears to 10-30 minutes, maintaining 4 to 8 hours; maximum IOP lowering effect occurs within about 75 minutes, maintaining 4-14 hours; it can alleviate or eliminate symptoms of glaucoma. It has selective direct effect on the M cholinergic receptors. Eye and most obvious effect is of the gland. It can cause miosis, decreased intraocular pressure, and a spasm effects. By exciting the pupil sphincter M cholinergic receptors, it can cause the pupil sphincter contraction. Miosis cause anterior chamber space to expand, it is easy to aqueous humor reflux, intraocular pressure decreased. 2-dimethylamino-methylfuran as furtrethonium iodide 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 furtrethonium iodide pharmaceutical intermediate 2-dimethylamino-methylfuran synthesis method , comprising the following steps: (i) equipped with a stirrer, a thermometer and a dropping funnel , the reaction vessel was added 1.6mol dimethylamine methanol solution (3), 500ml oxalic acid solution, 1.8 mol alumina, 2.1-2.6mol 2-furan dimethanol solution (2), controlling the stirring speed 130-170rpm, raised the solution temperature to 120—128 °C, continued the reaction for 5-8h, reducing the temperature of the solution to 90—96 °C, refluxed for 2-3h, added 130ml phosphoric acid solution after cooling, increased solution temperature to 60—66 °C, stirred for 90-130 min, added 300ml sodium sulfite solution, continued reaction for 80-110min, the temperature of the solution is reduced to 10-15 °C, added 110ml potassium hydrogen sulfite solution, allowed to stand for 3-5h, the solution appeared layer, separated the oil, the aqueous layer was extracted for 5-8 times with nitromethane solution, combined oil layer, dehydrated with dehydration agent, vacuum distillation, collecting fractions of 110—116 °C, recrystallized from toluene solution , got 2- dimethylamino-methylfuran (1); wherein, dimethylamine methanol solution in step (i) has a mass fraction of 70-75%; oxalic acid solution in step (i) has a mass fraction of 40-45%; 2-furan dimethanol solution in step (i) has a mass fraction of 80-85%; phosphoric acid solution in step (i) has a mass fraction of 35-40%; sodium sulfite solution in step (i) has a mass fraction of 25-30%, nitromethane solution in step (i) has a mass fraction of 65-70%; dehydration agent in step (i) is any one of anhydrous potassium carbonate or solid potassium hydroxide; vacuum distillation in step (i) has a pressure of 1.6-1.9kPa, toluene solution in step (i) has a mass fraction of 92-97%.
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, a thermometer and a dropping funnel, the reaction vessel was added 1.6mol dimethylamine methanol solution (3) with a mass fraction of 70%, 500ml oxalic acid solution with a mass fraction of 40%, 1.8 mol alumina, 2.1 mol 2-furan dimethanol solution (2) with a mass fraction of 80%, controlling the stirring speed 130 rpm, raised the solution temperature to 120 °C, continued the reaction for 5 h, reducing the temperature of the solution to 90 °C, refluxed for 2 h, added 130ml phosphoric acid solution with a mass fraction of 35% after cooling, increased solution temperature to 60 °C, stirred for 90 min, added 300ml sodium sulfite solution with a mass fraction of 25%, continued reaction for 80 min, the temperature of the solution is reduced to 10 °C, added 110ml potassium hydrogen sulfite solution, allowed to stand for 3h, the solution appeared layer, separated the oil, the aqueous layer was extracted for 5 times with nitromethane solution with a mass fraction of 65%, combined oil layer, dehydrated with anhydrous potassium carbonate dehydration agent, vacuum distillation with a pressure of 1.6 kPa , collecting fractions of 110—116 °C, recrystallized from toluene solution with a mass fraction of 92% , got 2- dimethylamino-methylfuran 158 g, yield 79%.
Embodiment 2
Equipped with a stirrer, a thermometer and a dropping funnel, the reaction vessel was added 1.6mol dimethylamine methanol solution (3) with a mass fraction of 72%, 500ml oxalic acid solution with a mass fraction of 42%, 1.8 mol alumina, 2.1 mol 2-furan dimethanol solution (2) with a mass fraction of 80%, controlling the stirring speed 150 rpm, raised the solution temperature to 123 °C, continued the reaction for 6 h, reducing the temperature of the solution to 92 °C, refluxed for 2 h, added 130ml phosphoric acid solution with a mass fraction of 37% after cooling, increased solution temperature to 62 °C, stirred for 110 min, added 300ml sodium sulfite solution with a mass fraction of 27%, continued reaction for 90 min, the temperature of the solution is reduced to 12 °C, added 110ml potassium hydrogen sulfite solution, allowed to stand for 3h, the solution appeared layer, separated the oil, the aqueous layer was extracted for 7 times with nitromethane solution with a mass fraction of 68%, combined oil layer, dehydrated with anhydrous potassium carbonate dehydration agent, vacuum distillation with a pressure of 1.7 kPa , collecting fractions of 110—116 °C, recrystallized from toluene solution with a mass fraction of 95% , got 2- dimethylamino-methylfuran 164 g, yield 82%.
Embodiment 3
Equipped with a stirrer, a thermometer and a dropping funnel, the reaction vessel was added 1.6mol dimethylamine methanol solution (3) with a mass fraction of 75%, 500ml oxalic acid solution with a mass fraction of 45%, 1.8 mol alumina, 2.1 mol 2-furan dimethanol solution (2) with a mass fraction of 85%, controlling the stirring speed 150 rpm, raised the solution temperature to 128 °C, continued the reaction for 6 h, reducing the temperature of the solution to 92 °C, refluxed for 2 h, added 130ml phosphoric acid solution with a mass fraction of 40% after cooling, increased solution temperature to 66 °C, stirred for 110 min, added 300ml sodium sulfite solution with a mass fraction of 27%, continued reaction for 90 min, the temperature of the solution is reduced to 15 °C, added 110ml potassium hydrogen sulfite solution, allowed to stand for 3h, the solution appeared layer, separated the oil, the aqueous layer was extracted for 8 times with nitromethane solution with a mass fraction of 68%, combined oil layer, dehydrated with solid potassium hydroxide dehydration agent, vacuum distillation with a pressure of 1.9 kPa , collecting fractions of 110—116 °C, recrystallized from toluene solution with a mass fraction of 97% , got 2- dimethylamino-methylfuran 172 g, yield 86%.
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. Furtrethonium iodide pharmaceutical intermediate 2- dimethylamino-methylfuran synthesis method , comprising the following steps: (i) equipped with a stirrer, a thermometer and a dropping funnel , the reaction vessel was added 1.6mol dimethylamine methanol solution (3), 500ml oxalic acid solution, 1.8 mol alumina, 2.1-2.6mol 2-furan dimethanol solution (2), controlling the stirring speed 130-170rpm, raised the solution temperature to 120—128 °C, continued the reaction for 5-8h, reducing the temperature of the solution to 90—96 °C, refluxed for 2-3h, added 130ml phosphoric acid solution after cooling, increased solution temperature to 60—66 °C, stirred for 90-130 min, added 300ml sodium sulfite solution, continued reaction for 80-110min, the temperature of the solution is reduced to 10 - 15 °C, added 110ml potassium hydrogen sulfite solution, allowed to stand for 3-5h, the solution appeared layer, separated the oil, the aqueous layer was extracted for 5-8 times with nitromethane solution, combined oil layer, dehydrated with dehydration agent, vacuum distillation, collecting fractions of 110—116 °C, recrystallized from toluene solution , got 2- dimethylamino-methylfuran (1); wherein, dimethylamine methanol solution in step (i) has a mass fraction of 70-75%; oxalic acid solution in step (i) has a mass fraction of 40-45%; 2-furan dimethanol solution in step (i) has a mass fraction of 80-85%; phosphoric acid solution in step (i) has a mass fraction of 35-40%; sodium sulfite solution in step (i) has a mass fraction of 25-30%, nitromethane solution in step (i) has a mass fraction of 65-70%.
2. Furtrethonium iodide pharmaceutical intermediate 2- dimethylamino-methylfuran synthesis method according to claim 1 wherein dehydration agent in step (i) is any one of anhydrous potassium carbonate or solid potassium hydroxide.
3. Furtrethonium iodide pharmaceutical intermediate 2- dimethylamino-methylfuran synthesis method according to claim 1 wherein vacuum distillation in step (i) has a pressure of 1.6-1.9kPa.
4. Furtrethonium iodide pharmaceutical intermediate 2- dimethylamino-methylfuran synthesis method according to claim 1 wherein toluene solution in step (i) has a mass fraction of 92-97%.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201511002907.2A CN105481804A (en) | 2015-12-25 | 2015-12-25 | Synthesis method of furtrethonium iodide drug intermediate 2-dimethylaminomethylfuran |
| CN2015110029072 | 2015-12-25 | ||
| CN2016108308698 | 2016-09-19 | ||
| CN201610830869.8A CN106432150A (en) | 2015-12-25 | 2016-09-19 | Synthetic method for furtrethonium iodide drug intermediate 2-dimethylamine methylfuran |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2016102309A4 true AU2016102309A4 (en) | 2017-02-23 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2016102309A Ceased AU2016102309A4 (en) | 2015-12-25 | 2016-12-24 | Furtrethonium iodide pharmaceutical intermediate 2- dimethylamino-methylfuran synthesis method |
Country Status (1)
| Country | Link |
|---|---|
| AU (1) | AU2016102309A4 (en) |
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2016
- 2016-12-24 AU AU2016102309A patent/AU2016102309A4/en not_active Ceased
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