AU2016102245A4 - Osalmide drug intermediates N- p-hydroxyphenyl salicylamide synthesis method - Google Patents
Osalmide drug intermediates N- p-hydroxyphenyl salicylamide synthesis method Download PDFInfo
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- AU2016102245A4 AU2016102245A4 AU2016102245A AU2016102245A AU2016102245A4 AU 2016102245 A4 AU2016102245 A4 AU 2016102245A4 AU 2016102245 A AU2016102245 A AU 2016102245A AU 2016102245 A AU2016102245 A AU 2016102245A AU 2016102245 A4 AU2016102245 A4 AU 2016102245A4
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Abstract
Osalmide drug intermediates N- p-hydroxyphenyl salicylamide synthesis method, comprising the following steps: the reaction vessel was added 0.07 mol p-aminophenol (3), 0.074-0.076mol 2- hydroxy benzamide (2), 70- 80ml ethyl acetate, controlling the stirring speed 110-150rpm, slowly added 0.031 mol stannous chloride , when color of the solution became dark, gradually heat up to 160-170 C after the addition, keep the reaction 5-6 h, distillation under reduced pressure, portion ethyl acetate was distilled off, the temperature of the solution is reduced to 35--38 C, the reaction solution was pour 500ml sodium bisulfite solution, allowed to stand, aqueous layer was added molecular sieves to decolorize, filtered and the filtrate was added oxalic acid solution, adjusted to pH 3-4, the precipitated solid was recrystallized from ethylene diamine solution, got white solid N-p-hydroxyphenyl salicylamide .
Description
Osalmide drug intermediates N- p-hydroxyphenyl salicylamide synthesis method
TECHNICAL FIELD
The present invention relates to osalmide drug intermediates N-p-hydroxyphenyl salicylamide synthesis method.
BACKGROUND ART
Osalmide drugs can inhibit the central nervous system and the hypothalamus in the synthesis of prostaglandins, antipyretic and analgesic effects outside; it can enhance the excitement of the cerebral cortex, the spirit, and combined with the anti-inflammatory drugs, and can enhance its antipyretic analgesic effect; by direct stimulation of a- adrenergic receptor function, it rarely cause central nervous system stimulant, but with selective upper respiratory capillary contraction, nasopharyngeal mucosa eliminate congestion, it can reduce the symptoms of nasal congestion effects; it can fight capillaries and increased capillary permeability caused by amines, reduce tearing, sneezing, runny nose and other allergy symptoms. N- p-hydroxyphenyl salicylamide as osalmide 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 osalmide drug intermediates N- p-hydroxyphenyl salicylamide synthesis method, comprising the following steps: (i) the reaction vessel was added 0.07 mol p-aminophenol (3), 0.074-0.076mol 2- hydroxy - benzamide (2), 70- 80ml ethyl acetate, controlling the stirring speed 110-150rpm, slowly added 0.031 mol stannous chloride , when color of the solution became dark, gradually heat up to 160—170 °C after the addition, keep the reaction 5-6 h, distillation under reduced pressure, portion ethyl acetate was distilled off, the temperature of the solution is reduced to 35—38 °C, the reaction solution was pour 500ml sodium bisulfite solution, allowed to stand, aqueous layer was added molecular sieves to decolorize, filtered and the filtrate was added oxalic acid solution, adjusted to pH 3-4, the precipitated solid was recrystallized from ethylene diamine solution , got white solid N- p-hydroxyphenyl salicylamide (1); wherein distillation under reduced pressure in step (i) has a pressure of 1.9-2.1kPa, sodium bisulfite solution in step (i) has a mass fraction of 20-25%, oxalic acid solution in step (i) has a mass fraction of 30-35%, ethylene diamine solution in step (i) has a mass fraction of 85-90%.
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
The reaction vessel was added 0.07 mol p-aminophenol (3), 0.074 mol 2- hydroxy - benzamide (2), 70 ml ethyl acetate, controlling the stirring speed 110 rpm, slowly added 0.031 mol stannous chloride , when color of the solution became dark, gradually heat up to 160 °C after the addition, keep the reaction 5 h, distillation under reduced pressure with a pressure of 1.9 kPa, portion ethyl acetate was distilled off, the temperature of the solution is reduced to 35 °C, the reaction solution was pour 500ml sodium bisulfite solution with a mass fraction of 20%, allowed to stand, aqueous layer was added molecular sieves to decolorize, filtered and the filtrate was added oxalic acid solution with a mass fraction of 30%, adjusted to pH 3, the precipitated solid was recrystallized from ethylene diamine solution with a mass fraction of 85% , got white solid N- p-hydroxyphenyl salicylamide 12.18 g, yield 76%.
Embodiment 2
The reaction vessel was added 0.07 mol p-aminophenol (3), 0.075 mol 2- hydroxy - benzamide (2), 75 ml ethyl acetate, controlling the stirring speed 140 rpm, slowly added 0.031 mol stannous chloride , when color of the solution became dark, gradually heat up to 165 °C after the addition, keep the reaction 5 h, distillation under reduced pressure with a pressure of 2.0 kPa, portion ethyl acetate was distilled off, the temperature of the solution is reduced to 36 °C, the reaction solution was pour 500ml sodium bisulfite solution with a mass fraction of 23%, allowed to stand, aqueous layer was added molecular sieves to decolorize, filtered and the filtrate was added oxalic acid solution with a mass fraction of 32%, adjusted to pH 3, the precipitated solid was recrystallized from ethylene diamine solution with a mass fraction of 87% , got white solid N- p-hydroxyphenyl salicylamide 12.66 g, yield 79%.
Embodiment 3
The reaction vessel was added 0.07 mol p-aminophenol (3), 0.076 mol 2- hydroxy - benzamide (2), 80 ml ethyl acetate, controlling the stirring speed 180 rpm, slowly added 0.031 mol stannous chloride , when color of the solution became dark, gradually heat up to 170 °C after the addition, keep the reaction 6 h, distillation under reduced pressure with a pressure of 2.1 kPa, portion ethyl acetate was distilled off, the temperature of the solution is reduced to 38 °C, the reaction solution was pour 500ml sodium bisulfite solution with a mass fraction of 23%, allowed to stand, aqueous layer was added molecular sieves to decolorize, filtered and the filtrate was added oxalic acid solution with a mass fraction of 33%, adjusted to pH 3, the precipitated solid was recrystallized from ethylene diamine solution with a mass fraction of 87% , got white solid N- p-hydroxyphenyl salicylamide 13.47 g, yield 84%.
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. Osalmide drug intermediates N- p-hydroxyphenyl salicylamide synthesis method, comprising the following steps: (i) the reaction vessel was added 0.07 mol p-aminophenol (3), 0.074-0.076mol 2- hydroxy - benzamide (2), 70- 80ml ethyl acetate, controlling the stirring speed 110-150rpm, slowly added 0.031 mol stannous chloride , when color of the solution became dark, gradually heat up to 160—170 °C after the addition, keep the reaction 5-6 h, distillation under reduced pressure, portion ethyl acetate was distilled off, the temperature of the solution is reduced to 35—38 °C, the reaction solution was pour 500ml sodium bisulfite solution, allowed to stand, aqueous layer was added molecular sieves to decolorize, filtered and the filtrate was added oxalic acid solution, adjusted to pH 3-4, the precipitated solid was recrystallized from ethylene diamine solution , got white solid N- p-hydroxyphenyl salicylamide (1); wherein distillation under reduced pressure in step (i) has a pressure of 1.9-2.1kPa.
2. Osalmide drug intermediates N- p-hydroxyphenyl salicylamide synthesis method according to claim 1 wherein sodium bisulfite solution in step (i) has a mass fraction of 20-25%.
3. Osalmide drug intermediates N- p-hydroxyphenyl salicylamide synthesis method according to claim 1 wherein oxalic acid solution in step (i) has a mass fraction of 30-35%.
4. Osalmide drug intermediates N- p-hydroxyphenyl salicylamide synthesis method according to claim 1 wherein ethylene diamine solution in step (i) has a mass fraction of 85-90%.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2015109827917 | 2015-12-24 | ||
| CN201510982791.7A CN105503633A (en) | 2015-12-24 | 2015-12-24 | Synthesis method of oxophenamide drug intermediate N-(p-hydroxyphenyl)salicylamide |
| CN201610814139.9A CN106397247A (en) | 2015-12-24 | 2016-09-11 | Synthesis method of intermediate N-p-hydroxyphenyl salicylamide of oxophenamide drug |
| CN2016108141399 | 2016-09-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2016102245A4 true AU2016102245A4 (en) | 2017-02-16 |
Family
ID=57996390
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2016102245A Ceased AU2016102245A4 (en) | 2015-12-24 | 2016-12-23 | Osalmide drug intermediates N- p-hydroxyphenyl salicylamide synthesis method |
Country Status (1)
| Country | Link |
|---|---|
| AU (1) | AU2016102245A4 (en) |
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2016
- 2016-12-23 AU AU2016102245A patent/AU2016102245A4/en not_active Ceased
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| FGI | Letters patent sealed or granted (innovation patent) | ||
| MK22 | Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry |