AU2016102273A4 - Bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-1-phenyl-acetone synthesis method - Google Patents
Bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-1-phenyl-acetone synthesis method Download PDFInfo
- Publication number
- AU2016102273A4 AU2016102273A4 AU2016102273A AU2016102273A AU2016102273A4 AU 2016102273 A4 AU2016102273 A4 AU 2016102273A4 AU 2016102273 A AU2016102273 A AU 2016102273A AU 2016102273 A AU2016102273 A AU 2016102273A AU 2016102273 A4 AU2016102273 A4 AU 2016102273A4
- Authority
- AU
- Australia
- Prior art keywords
- solution
- diethylamino
- phenyl
- mass
- added
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Abstract
Bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-1-phenyl-acetone synthesis method, comprising the following steps: equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 0.23mol a - amine propiophenone (2), slowly added 0.51-0.53mol diethylamine (3), increased solution temperature to 85-90 C, continued the reaction for 60-90 min, reduced the temperature of solution to 60--65 C, 120ml toluene solution was added, controlled stirring speed 130-150 rpm, stirred for 60-80 min, filtered, and the filtrate was washed with oxalic acid solution, the combined extracts was added potassium sulfite solution, adjusted pH to 8-9 , extracted 5-7 times with nitromethane solution, reduced the solution temperature to 5-9 C, precipitated crystals were filtered, washed with salt solution, washed with acetonitrile solution, recrystallized from cyclohexane solution, got 2-diethylamino- 1 -phenyl-acetone.
Description
2016102273 24 Dec 2016 1
Bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-l-phenyl-acetone synthesis method
TECHNICAL FIELD
The present invention relates to bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-l-phenyl-acetone synthesis method.
BACKGROUND ART
Bupropion hydrochloride have weak inhibition of 5-HT, dopamine reuptake, but has no effect on monoamine oxidase. Bupropion is a racemic mixture. Pharmacological activity and pharmacokinetics of the enantiomers has not been studied kinetics single. Bupropion pharmacokinetic profile showed two compartment model. The average half-life of terminal phase is 21 hours (± 20%), the average distribution phase half-life is 3-4 hours. Absorption: after only a small fraction of bupropion oral medication can be absorbed, reaching peak plasma concentrations within 2 hours. In vitro tests showed that the concentration of plasma protein concentration is 200pg / mL when combined rate is 84%. Hydroxyl metabolite of bupropion protein binding rate with bupropion is similar to the other metabolites threonine hydrogenated bupropion protein binding rate is only half of his amphetamine ketone. 2016102273 24 Dec 2016 2 2-diethylamino-l-phenyl-acetone as bupropion hydrochloride 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 bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-l-phenyl-acetone synthesis method, comprising the following steps: (i) equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 0.23mola - amine propiophenone (2), slowly added 0.51 -0.53mol diethylamine (3), increased solution temperature to 85—90 °C, continued the reaction for 60-90 min, reduced the temperature of solution to 60—65 °C, 120ml toluene solution was added, controlled stirring speed 130-150 rpm, stirred for 60-80 min, filtered, and the filtrate was washed with oxalic acid solution, the combined extracts was added potassium sulfite solution, adjusted pH to 8-9 , extracted 5-7 times with nitromethane solution, reduced the solution temperature to 5—9 °C, precipitated crystals were 2016102273 24 Dec 2016 / \ 3 filtered, washed with salt solution, washed with acetonitrile solution, recrystallized from cyclohexane solution, got 2-diethylamino-l-phenyl-acetone (1 ); wherein, toluene solution in step (i) has a mass of 65-70%, oxalic acid solution in step (i) has a mass of 25-30%, potassium sulfite solution in step (i) has a mass of 40-45%, nitromethane solution in step (i) has a mass of 60-65%, salt solution in step (i) is any one of potassium bromide solution or sodium sulfate solution; acetonitrile solution in step (i) has a mass of 75-80%; cyclohexane solution in step (i) has a mass of 90-95%.
The throughout reaction process can be summarized using the following reaction formula:
HjCHCT 1 C2Hs ^ ^ VH iN ft C2Hs (2) (3) ch2ch2—N· „c. 2016102273 24 Dec 2016 4
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, a reflux condenser and a dropping funnel, the reaction vessel was added 0.23mola - amine propiophenone (2), slowly added 0.51mol diethylamine (3), increased solution temperature to 85 °C, continued the reaction for 60 min, reduced the temperature of solution to 60 °C, 120ml toluene solution with a mass of 65% was added, controlled stirring speed 130 rpm, stirred for 60 min, filtered, and the filtrate was washed with oxalic acid solution with a mass of 25% , the combined extracts was added potassium sulfite solution with a mass of 40%, adjusted pH to 8 , extracted 5 times with nitromethane solution with a mass of 60 %, reduced the solution temperature to 5°C, precipitated crystals were filtered, washed with potassium bromide solution, washed with acetonitrile solution with a mass of 75 %, recrystallized from cyclohexane solution with a mass of 90 %, got 2-diethylamino-l-phenyl-acetone 38.38 g, yield 81%. 2016102273 24 Dec 2016 5
Embodiment 2
Equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 0.23mola - amine propiophenone (2), slowly added 0.52mol diethylamine (3), increased solution temperature to 87 °C, continued the reaction for 62 min, reduced the temperature of solution to 62 °C, 120ml toluene solution with a mass of 67% was added, controlled stirring speed 140 rpm, stirred for 70 min, filtered, and the filtrate was washed with oxalic acid solution with a mass of 27% , the combined extracts was added potassium sulfite solution with a mass of 42%, adjusted pH to 8 , extracted 6 times with nitromethane solution with a mass of 60 %, reduced the solution temperature to 7°C, precipitated crystals were filtered, washed with sodium sulfate solution, washed with acetonitrile solution with a mass of 78 %, recrystallized from cyclohexane solution with a mass of 93 %, got 2-diethylamino-l-phenyl-acetone 40.27 g, yield 85%. 2016102273 24 Dec 2016 6
Embodiment 3
Equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 0.23mola - amine propiophenone (2), slowly added 0.53mol diethylamine (3), increased solution temperature to 90 °C, continued the reaction for 90 min, reduced the temperature of solution to 65 °C, 120ml toluene solution with a mass of 70% was added, controlled stirring speed 150 rpm, stirred for 80 min, filtered, and the filtrate was washed with oxalic acid solution with a mass of 30% , the combined extracts was added potassium sulfite solution with a mass of 45%, adjusted pH to 9 , extracted 7 times with nitromethane solution with a mass of 65 %, reduced the solution temperature to 9°C, precipitated crystals were filtered, washed with sodium sulfate solution, washed with acetonitrile solution with a mass of 80 %, recrystallized from cyclohexane solution with a mass of 95 %, got 2-diethylamino-l-phenyl-acetone 43.12 g, yield 91%. 2016102273 24 Dec 2016 7
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. Bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-l-phenyl-acetone synthesis method, comprising the following steps: (i) equipped with a stirrer, a thermometer, a reflux condenser and a dropping funnel, the reaction vessel was added 0.23mola - amine propiophenone (2), slowly added 0.51-0.53mol diethylamine (3), increased solution temperature to 85—90 °C, continued the reaction for 60-90 min, reduced the temperature of solution to 60—65 °C, 120ml toluene solution was added, controlled stirring speed 130-150 rpm, stirred for 60-80 min, filtered, and the filtrate was washed with oxalic acid solution, the combined extracts was added potassium sulfite solution, adjusted pH to 8-9 , extracted 5-7 times with nitromethane solution, reduced the solution temperature to 5—9 °C, precipitated crystals were filtered, washed with salt solution, washed with acetonitrile solution, recrystallized from cyclohexane solution, got 2-diethylamino-l-phenyl-acetone (1 ); wherein, toluene solution in step (i) has a mass of 65-70%, oxalic acid solution in step (i) has a mass of 25-30%, potassium sulfite solution in step (i) has a mass of 40-45%, nitromethane solution in step (i) has a mass of 60-65%.
2. Bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-l-phenyl-acetone synthesis method according to claim 1 wherein salt solution in step (i) is any one of potassium bromide solution or sodium sulfate solution.
3. Bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-l-phenyl-acetone synthesis method according to claim 1 wherein acetonitrile solution in step (i) has a mass of 75-80%.
4. Bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-l-phenyl-acetone synthesis method according to claim 1 wherein cyclohexane solution in step (i) has a mass of 90-95%.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2015109892564 | 2015-12-24 | ||
| CN201510989256.4A CN105461577A (en) | 2015-12-24 | 2015-12-24 | Synthesis method of amfepramone hydrochloride drug intermediate 2-diethylamino-1-phenylacetone |
| CN2016108240479 | 2016-09-14 | ||
| CN201610824047.9A CN106431944A (en) | 2015-12-24 | 2016-09-14 | Synthetic method of 2-diethylin-1-phenylacetone as amfepramone hydrochloride drug intermediate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2016102273A4 true AU2016102273A4 (en) | 2017-02-23 |
Family
ID=58046338
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2016102273A Ceased AU2016102273A4 (en) | 2015-12-24 | 2016-12-24 | Bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-1-phenyl-acetone synthesis method |
Country Status (1)
| Country | Link |
|---|---|
| AU (1) | AU2016102273A4 (en) |
-
2016
- 2016-12-24 AU AU2016102273A patent/AU2016102273A4/en not_active Ceased
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP4282416A3 (en) | Process of manufacture of a compound for inhibiting the activity of shp2 | |
| US8222454B2 (en) | Process for preparing optical pure milnacipran and its pharmaceutically accepted salts | |
| WO2010116140A8 (en) | New process for preparing hydroxylamines and medicaments | |
| US8138377B2 (en) | Arylbicyclo[3.1.0]hexylamines and methods and compositions for their preparation and use | |
| EP2427183A2 (en) | Therapeutic compounds | |
| AU2016102273A4 (en) | Bupropion hydrochloride pharmaceutical intermediate 2-diethylamino-1-phenyl-acetone synthesis method | |
| EP3156391A1 (en) | Method for preparing sitagliptin intermediate via asymmetrical reduction method | |
| US8378143B2 (en) | Methods of making Efavirens and intermediates thereof | |
| US20120289744A1 (en) | Process for preparing optically pure milnacipran and its pharmaceutically acceptable salts | |
| NZ612592A (en) | Process for the enzymatic synthesis of (7s)-1-(3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl) n-methyl methanamine, and application in the synthesis of ivabradine and salts thereof | |
| WO2018143165A1 (en) | Method for producing optically active pyrrolidine compounds | |
| US20120184774A1 (en) | Process for the preparation of pharmaceutically acceptable salts of racemic milnacipran and its optical enantiomers thereof | |
| AU2016102188A4 (en) | Pyrazolone drug intermediates acetyl acetanilide synthesis method | |
| AU2016102258A4 (en) | Olanzapine pharmaceutical intermediate 2-(o-nitrophenyl) -3-cyano-5-methyl-thiophene synthesis method | |
| TW200916092A (en) | N-oxides of venlafaxine and O-desmethylvenlafaxine as prodrugs | |
| US10214480B2 (en) | Synthesis process for chiral cyclopropyl ethynyl tertiary alcohol compound | |
| AU2016102290A4 (en) | Antitussive drug intermediates benzyl acetone synthesis method | |
| CN103709095B (en) | The preparation method of 4-cyclic lactam base aniline | |
| AU2016102283A4 (en) | Astemizole drug intermediates N-(4-fluorobenzyl) phthalimide synthesis method | |
| EP2649044B1 (en) | Method for synthesising substituted aminocyclohexanone derivatives | |
| Hu et al. | Chiral bifunctional organocatalysts for enantioselective synthesis of 3-substituted isoindolinones | |
| AU2016102262A4 (en) | Guaifenesin pharmaceutical intermediate 3- (o-methoxyphenoxy) -1,2-propanediol synthesis method | |
| AU2016102275A4 (en) | Granisetron drug intermediates 1-methyl-indole-3-carboxylic acid synthesis method | |
| AU2016102263A4 (en) | Nafcillin sodium drug intermediates 2-ethoxy naphthalene synthesis method | |
| AU2016102244A4 (en) | Balsalazide drug intermediates nitrobenzoylhydrazone -β- alanine synthesis method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGI | Letters patent sealed or granted (innovation patent) | ||
| MK22 | Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry |