CN112661659A - Preparation process of bupropion hydrochloride - Google Patents
Preparation process of bupropion hydrochloride Download PDFInfo
- Publication number
- CN112661659A CN112661659A CN202110020684.1A CN202110020684A CN112661659A CN 112661659 A CN112661659 A CN 112661659A CN 202110020684 A CN202110020684 A CN 202110020684A CN 112661659 A CN112661659 A CN 112661659A
- Authority
- CN
- China
- Prior art keywords
- bupropion hydrochloride
- reaction
- molar ratio
- hydrochloric acid
- steps
- 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.)
- Pending
Links
- IKBZAUYPBWFMDI-UHFFFAOYSA-N 5-bromo-4-methoxy-7-methyl-2,3-dihydro-1h-indene Chemical compound C1=C(Br)C(OC)=C2CCCC2=C1C IKBZAUYPBWFMDI-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 229960004367 bupropion hydrochloride Drugs 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 13
- PQWGFUFROKIJBO-UHFFFAOYSA-N 1-(3-chlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=CC(Cl)=C1 PQWGFUFROKIJBO-UHFFFAOYSA-N 0.000 claims abstract description 10
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims abstract description 10
- 230000008569 process Effects 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- 239000000047 product Substances 0.000 claims description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 239000012043 crude product Substances 0.000 claims description 9
- 239000012295 chemical reaction liquid Substances 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 7
- 239000008213 purified water Substances 0.000 claims description 7
- 238000000967 suction filtration Methods 0.000 claims description 7
- 238000001704 evaporation Methods 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 230000008020 evaporation Effects 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 238000007670 refining Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 abstract description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052794 bromium Inorganic materials 0.000 abstract description 4
- 238000005893 bromination reaction Methods 0.000 abstract description 3
- 238000005660 chlorination reaction Methods 0.000 abstract description 3
- 230000001988 toxicity Effects 0.000 abstract description 3
- 231100000419 toxicity Toxicity 0.000 abstract description 3
- 230000007547 defect Effects 0.000 abstract description 2
- 238000005576 amination reaction Methods 0.000 abstract 1
- 238000007254 oxidation reaction Methods 0.000 abstract 1
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 230000005586 smoking cessation Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229960001058 bupropion Drugs 0.000 description 1
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 229940053544 other antidepressants in atc Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Images
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation process of bupropion hydrochloride. Most of the existing methods for preparing bupropion hydrochloride adopt bromination reaction, and bromine has strong toxicity and corrosiveness. In order to overcome the defects, the invention provides a novel preparation process of bupropion hydrochloride, which adopts hydrochloric acid with the concentration of 30% to replace bromine for reaction. The method of the process comprises the following steps: carrying out oxidation reaction on 30% hydrochloric acid and hydrogen peroxide to obtain an intermediate 1; the intermediate 1 and m-chloropropiophenone are subjected to chlorination reaction to obtain an intermediate 2; the intermediate 2 further reacts with tert-butylamine to generate amination reaction to obtain an intermediate 3; and finally, salifying and purifying the intermediate 3 to obtain a pure target bupropion hydrochloride product.
Description
Technical Field
The invention belongs to the field of pharmaceutical chemistry, and particularly relates to a preparation process of bupropion hydrochloride.
Background
Bupropion hydrochloride is an aminoketone antidepressant, is also the only market variety of the current antidepressant drugs, and is successfully developed by the American Baowei company in the 70 s as a selective depression preparation of dopamine transmitter. The bupropion hydrochloride belongs to central nervous system medication, has weak inhibition effect on reuptake of norepinephrine, 5-HT and dopamine, and has no effect on monoamine oxidase. The antidepressant action mechanism of the product is not clear, and may be related to the action of norepinephrine and/or dopaminergic, but the effect of bupropion is stronger than that of other antidepressants. In addition, bupropion hydrochloride was first marketed in 1997 in the united states as an aid for smoking cessation, which was the first non-nicotine prescription drug on the U.S. market for smoking cessation.
Bupropion hydrochloride is a racemic mixture and thus the pharmacological activity and pharmacokinetics of the individual enantiomers have not been studied. The pharmacokinetic curve of bupropion hydrochloride is in a two-chamber model, the mean half-life of the terminal phase is 21 hours (+ -20%), and the mean half-life of the distribution phase is 3-4 hours. Only a small fraction of the drug can be absorbed after oral administration, reaching peak blood concentration within 2 hours.
Most of the existing methods for preparing bupropion hydrochloride adopt bromination reaction, and bromine has strong toxicity and corrosiveness. In order to overcome the defects, the invention provides a novel preparation process of bupropion hydrochloride, which adopts hydrochloric acid to replace bromine for reaction.
Disclosure of Invention
The invention aims to provide a preparation process of bupropion hydrochloride, which aims to solve the problems in the background technology.
A preparation process of bupropion hydrochloride comprises the following steps:
(1) adding hydrogen peroxide into hydrochloric acid, wherein the reaction molar ratio of the hydrochloric acid to the hydrogen peroxide is 1-1.2, controlling the temperature at 20-30 ℃, and reacting to obtain an intermediate 1 reaction solution;
(2) adding m-chloropropiophenone into the reaction liquid of the intermediate 1, wherein the reaction molar ratio of the intermediate 1 to the m-chloropropiophenone is 1-1.3, controlling the temperature to be 60-65 ℃ for reaction to obtain reaction liquid of an intermediate 2, extracting the intermediate 2 from the reaction liquid of the intermediate 2, and leaving extract liquid of the intermediate 2 for later use;
(3) under the condition of stirring at room temperature, adding tert-butylamine into the intermediate 2 extract, wherein the reaction molar ratio of the intermediate 2 to the tert-butylamine is 1-9, after the reaction is finished, adding purified water for stirring, standing for layering, and removing a water layer to obtain an intermediate 3 extract; evaporating the intermediate 3 extract to dryness at normal pressure, and dissolving in organic solvent to obtain intermediate 3 solution;
(4) salifying the intermediate 3 to obtain a crude bupropion hydrochloride product;
(5) refining the bupropion hydrochloride crude product to obtain a bupropion hydrochloride pure product;
preferably, the step (4) is specifically: cooling the intermediate 3 solution to 0-5 ℃, and adding hydrochloric acid, wherein the salifying molar ratio of the intermediate 3 to the hydrochloric acid is 1-1.8; adjusting the pH value to 2-3, stirring, carrying out suction filtration and evaporation to dryness to obtain a crude bupropion hydrochloride product.
Preferably, the step (5) is specifically: adding purified water into the bupropion hydrochloride crude product, wherein the weight ratio of the bupropion hydrochloride crude product to the water is 1-6; stirring and heating to 80-85 ℃, keeping the temperature to dissolve and clear, cooling to 10-15 ℃ for crystallization, and performing suction filtration and drying to obtain a pure bupropion hydrochloride product.
Preferably, the reaction molar ratio of the hydrochloric acid to the hydrogen peroxide in the step (1) is 1-1.1.
Preferably, the reaction molar ratio of the intermediate 1 to the m-chloropropiophenone in the step (2) is 1-1.1.
Preferably, the reaction molar ratio of the intermediate 2 to the tert-butylamine in the step (3) is 1-7.
Preferably, the salifying molar ratio of the intermediate 3 to the hydrochloric acid in the step (4) is 1-1.2.
Preferably, the weight ratio of the crude bupropion hydrochloride product to the water in the step (5) is 1-4.
Preferably, the extraction solvent used in step (2) is one or both of dichloromethane and toluene.
Preferably, the organic solvent in step (3) is one or more of dichloromethane, chloroform and toluene.
Compared with the prior art, the invention has the beneficial effects that:
(1) according to the preparation process of bupropion hydrochloride provided by the invention, the adopted raw materials are low in toxicity and corrosivity, and the pollution of the traditional bromination reaction to the environment is reduced;
(2) the preparation process of bupropion hydrochloride provided by the invention has the advantages of high chlorination reaction rate, less impurities and high yield.
Drawings
FIG. 1 is a scheme showing the synthesis of bupropion hydrochloride according to the present invention;
description of reference numerals: 1. intermediate 1; 2. intermediate 2; 3. intermediate 3.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below with reference to fig. 1 of the specification, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
Step (1): adding 41g of hydrochloric acid (0.38mol) with the concentration of 30% into a reaction bottle, dropwise adding 46g of hydrogen peroxide (0.456mol) at the temperature of 20-30 ℃, finishing dropwise adding within 4 hours, and reacting for 8 hours after dropwise adding to obtain an intermediate 1 reaction solution, wherein the calculated molar yield is 95%.
Step (2): heating the reaction liquid of the intermediate 1 to 65 ℃, adding 38g of m-chloropropiophenone (0.226mol) through an oscillating feeder, and carrying out chlorination reaction on the m-chloropropiophenone in the intermediate 1; controlling the temperature at 60-65 ℃, reacting for 4 hours, cooling to 10-15 ℃, adding 50ml of dichloromethane for extraction and layering, and extracting to obtain an intermediate 2 extract; 20ml of purified water was added to the intermediate 2 extract for washing, and after washing, the intermediate 2 extract was left for further use.
And (3): under the condition of room temperature, 138g of tert-butylamine (1.9mol) is added into the extract liquor of the intermediate 2 while stirring, after 24 hours of reaction, 100ml of purified water is added and stirred for 10 minutes; standing for layering, and removing a water layer to obtain an intermediate 3 extract; and (3) evaporating the intermediate 3 extract to dryness at normal pressure, adding 200ml of isopropanol solution, and stirring for 1h until the solution is clear to obtain an intermediate 3 solution.
And (4): and (3) cooling the intermediate 3 solution to 0-5 ℃, adding hydrochloric acid with the concentration of 30%, adjusting the pH to 2-3, stirring for 4h, performing suction filtration, and drying the product obtained by suction filtration for 12h to obtain 40g of bupropion hydrochloride crude product.
And (5): taking 40g of bupropion hydrochloride crude product, adding 240ml of purified water, heating the solution to 80-85 ℃ while stirring, preserving heat for 1h, cooling to 10-15 ℃ for crystallization for 4h, carrying out suction filtration and drying on the obtained crystals to obtain 38g of bupropion hydrochloride pure product, wherein the calculated molar yield is 95%.
Examples 2 to 4
The reaction is the same as the example 1 except that the reaction molar ratio of the 30 percent hydrochloric acid to the hydrogen peroxide in the step (1) is different from the example 1.
| Reaction molar ratio of 30% hydrochloric acid to hydrogen peroxide | Yield of |
| 0.38mol：0.494mol | 92.4％ |
| 0.38mol：0.418mol | 94.6％ |
| 0.38mol：0.38mol | 90.2％ |
Examples 5 to 7
The reaction was carried out in the same manner as in example 1 except that the reaction molar ratio of the intermediate 1 to m-chloropropiophenone in step (2) was changed from that in example 1.
Examples 8 to 10
The reaction is the same as example 1 except that the molar ratio of the intermediate 2 to tert-butylamine in step (3) is different from that in example 1.
| Reaction molar ratio of intermediate 2 to tert-butylamine | Yield of |
| 0.38mol：1.9mol | 95％ |
| 0.27mol：1.9mol | 99.2％ |
| 0.21mol：1.9mol | 97.2％ |
Examples 11 to 13
The same procedure as in example 1 was repeated except that the reaction molar ratio of the intermediate 3 to 30% hydrochloric acid in step (4) was changed from that in example 1.
| Reaction molar ratio of intermediate 3 to 30% hydrochloric acid | Yield of |
| 0.208mol：0.229mol | 85.4％ |
| 0.208mol：0.25mol | 90.5％ |
| 0.208mol：0.27mol | 87.2％ |
Examples 14 to 16
The process is the same as example 1 except that the weight ratio of the crude bupropion hydrochloride product to water in step (5) is different from that in example 1.
| Weight ratio of bupropion hydrochloride crude product to water | Yield of |
| 40g：160g | 91.6％ |
| 40g：240g | 95％ |
| 40g：320g | 90％ |
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (10)
1. A preparation process of bupropion hydrochloride is characterized by comprising the following steps:
(1) adding hydrogen peroxide into hydrochloric acid, wherein the reaction molar ratio of the hydrochloric acid to the hydrogen peroxide is 1-1.2, controlling the temperature at 20-30 ℃, and reacting to obtain an intermediate 1 reaction solution;
(2) adding m-chloropropiophenone into the reaction liquid of the intermediate 1, wherein the reaction molar ratio of the intermediate 1 to the m-chloropropiophenone is 1-1.3, controlling the temperature to be 60-65 ℃ for reaction to obtain reaction liquid of an intermediate 2, extracting the intermediate 2 from the reaction liquid of the intermediate 2, and leaving extract liquid of the intermediate 2 for later use;
(3) under the condition of stirring at room temperature, adding tert-butylamine into the intermediate 2 extract, wherein the reaction molar ratio of the intermediate 2 to the tert-butylamine is 1-9, after the reaction is finished, adding purified water for stirring, standing for layering, and removing a water layer to obtain an intermediate 3 extract; evaporating the intermediate 3 extract to dryness at normal pressure, and dissolving in organic solvent to obtain intermediate 3 solution;
(4) salifying the intermediate 3 to obtain a crude bupropion hydrochloride product;
(5) and (4) refining the crude bupropion hydrochloride product to obtain a pure bupropion hydrochloride product.
2. The preparation process of bupropion hydrochloride according to claim 1, wherein the step (4) is specifically: cooling the intermediate 3 solution to 0-5 ℃, and adding hydrochloric acid, wherein the salifying molar ratio of the intermediate 3 to the hydrochloric acid is 1-1.8; adjusting the pH value to 2-3, stirring, carrying out suction filtration and evaporation to dryness to obtain a crude bupropion hydrochloride product.
3. The process for preparing bupropion hydrochloride according to claim 1, wherein the step (5) is specifically as follows: adding purified water into the bupropion hydrochloride crude product, wherein the weight ratio of the bupropion hydrochloride crude product to the water is 1-6; stirring and heating to 80-85 ℃, keeping the temperature to dissolve and clear, cooling to 10-15 ℃ for crystallization, and performing suction filtration and drying to obtain a pure bupropion hydrochloride product.
4. The process of claim 1, wherein the step of preparing bupropion hydrochloride comprises the following steps: the reaction molar ratio of the hydrochloric acid to the hydrogen peroxide in the step (1) is 1-1.1.
5. The process of claim 1, wherein the step of preparing bupropion hydrochloride comprises the following steps: in the step (2), the reaction molar ratio of the intermediate 1 to the m-chloropropiophenone is 1-1.1.
6. The process of claim 1, wherein the step of preparing bupropion hydrochloride comprises the following steps: the reaction molar ratio of the intermediate 2 to the tert-butylamine in the step (3) is 1-7.
7. The process of claim 2, wherein the step of preparing bupropion hydrochloride comprises the following steps: in the step (4), the salifying molar ratio of the intermediate 3 to 30% hydrochloric acid is 1-1.2.
8. The process of claim 1, wherein the step of preparing bupropion hydrochloride comprises the following steps: the weight ratio of the bupropion hydrochloride crude product to the water in the step (5) is 1-4.
9. The process of claim 1, wherein the step of preparing bupropion hydrochloride comprises the following steps: the extraction solvent used in the step (2) is one or two of dichloromethane and toluene.
10. The process of claim 1, wherein the step of preparing bupropion hydrochloride comprises the following steps: in the step (3), the organic solvent is one or more than two of dichloromethane, chloroform and toluene.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110020684.1A CN112661659A (en) | 2021-01-08 | 2021-01-08 | Preparation process of bupropion hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110020684.1A CN112661659A (en) | 2021-01-08 | 2021-01-08 | Preparation process of bupropion hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112661659A true CN112661659A (en) | 2021-04-16 |
Family
ID=75413533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110020684.1A Pending CN112661659A (en) | 2021-01-08 | 2021-01-08 | Preparation process of bupropion hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112661659A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101088985A (en) * | 2007-07-06 | 2007-12-19 | 浙江普洛医药科技有限公司 | Amfebutamone hydrochloride synthesizing process |
| CN101407469A (en) * | 2007-10-12 | 2009-04-15 | 浙江京新药业股份有限公司 | Preparation method of bupropion hydrochloride |
| CN101888988A (en) * | 2007-11-27 | 2010-11-17 | 埃吉斯药物股份公开有限公司 | The method for preparing pharmaceutical intermediate |
| CN105968023A (en) * | 2015-09-22 | 2016-09-28 | 威海迪素制药有限公司 | Method for preparing bupropion hydrochloride |
| CN108558686A (en) * | 2018-04-12 | 2018-09-21 | 绍兴文理学院元培学院 | A kind of preparation method of BUPROPIONE HCl |
-
2021
- 2021-01-08 CN CN202110020684.1A patent/CN112661659A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101088985A (en) * | 2007-07-06 | 2007-12-19 | 浙江普洛医药科技有限公司 | Amfebutamone hydrochloride synthesizing process |
| CN101407469A (en) * | 2007-10-12 | 2009-04-15 | 浙江京新药业股份有限公司 | Preparation method of bupropion hydrochloride |
| CN101888988A (en) * | 2007-11-27 | 2010-11-17 | 埃吉斯药物股份公开有限公司 | The method for preparing pharmaceutical intermediate |
| CN105968023A (en) * | 2015-09-22 | 2016-09-28 | 威海迪素制药有限公司 | Method for preparing bupropion hydrochloride |
| CN108558686A (en) * | 2018-04-12 | 2018-09-21 | 绍兴文理学院元培学院 | A kind of preparation method of BUPROPIONE HCl |
Non-Patent Citations (1)
| Title |
|---|
| BRUCE L. JENSEN ET AL.: "Kinetic Studies and Stereochemical Considerations for the Rearrangement of 1 -(o -Chlorophenyl) -2-bromo-2-chIoro-1 -propylTrifluoroacetate", 《J. ORG. CHEM.》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101337897B (en) | Process for preparing ambroxol, analogue thereof or salts thereof | |
| CN115073312B (en) | Synthesis method of norepinephrine bitartrate | |
| WO2017096772A1 (en) | Method for preparing anti-heart-failure medicine lcz696 | |
| CN105294477A (en) | Method for preparing lidocaine hydrochloride | |
| CN110041261A (en) | A kind of preparation method of naphcon | |
| JPS5825656B2 (en) | Dopamine energy production | |
| US20040242887A1 (en) | Deuterated n-substituted and alpha-substituted diphenylalkoxy acetic acid amino alkyl esters and medicaments containing these compounds | |
| CN102229538B (en) | Method for synthesizing dapoxetine | |
| CN112661659A (en) | Preparation process of bupropion hydrochloride | |
| CN106588753B (en) | Pimanerin preparation method | |
| WO2010046360A1 (en) | Process for the preparation of substantially optically pure repaglinide and precursors thereof | |
| CN110950795A (en) | N-ethylpyridine methylamine methanesulfonate crystal, preparation process and application thereof in preparation of tropicamide | |
| CN108558686B (en) | Preparation method of bupropion hydrochloride | |
| CN114728952B (en) | Lurasidone salt process for preparing acid salts | |
| CN112279817B (en) | Preparation method of high-purity pramipexole dihydrochloride | |
| CN109678737B (en) | Preparation method of pregabalin | |
| WO2005121066A1 (en) | The preparation method of (1 r,2s)-(-)-ephedrine or its hydrochloride | |
| CN101407469A (en) | Preparation method of bupropion hydrochloride | |
| CN104326927B (en) | A kind of preparation method of 1-[2-amino-1-(4-methoxyphenyl) ethyl] Hexalin sulfate | |
| CN107011137B (en) | Synthetic method of pimavanserin intermediate | |
| CN113444001B (en) | Ambroxol hydrochloride production process | |
| CN113912545B (en) | Method for synthesizing and refining naphazoline inorganic acid salt | |
| CN113264839B (en) | Method for preparing levo-terbutaline by using chiral prosthetic group | |
| CN114163415B (en) | Preparation method of duloxetine hydrochloride intermediate | |
| CN116496234B (en) | Preparation method of urapidil hydrochloride key intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210416 |
|
| RJ01 | Rejection of invention patent application after publication |