CN116348110A - Paroxetine hydrochloride purification method - Google Patents
Paroxetine hydrochloride purification method Download PDFInfo
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- CN116348110A CN116348110A CN202180066909.5A CN202180066909A CN116348110A CN 116348110 A CN116348110 A CN 116348110A CN 202180066909 A CN202180066909 A CN 202180066909A CN 116348110 A CN116348110 A CN 116348110A
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- Prior art keywords
- paroxetine hydrochloride
- paroxetine
- solvent
- acid
- filtering
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- 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.)
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- AHOUBRCZNHFOSL-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidine Chemical compound C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 title claims abstract description 96
- 229960005183 paroxetine hydrochloride Drugs 0.000 title claims abstract description 47
- 238000000034 method Methods 0.000 title claims abstract description 37
- 238000000746 purification Methods 0.000 title abstract description 15
- 238000001914 filtration Methods 0.000 claims abstract description 23
- 238000003756 stirring Methods 0.000 claims abstract description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000001816 cooling Methods 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 13
- 238000001035 drying Methods 0.000 claims abstract description 12
- 238000010438 heat treatment Methods 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 8
- 238000002425 crystallisation Methods 0.000 claims abstract description 3
- 230000008025 crystallization Effects 0.000 claims abstract description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 claims description 13
- 229960002296 paroxetine Drugs 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 1
- 239000011707 mineral Substances 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000000706 filtrate Substances 0.000 description 9
- 239000000843 powder Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000008213 purified water Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 239000012535 impurity Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000010413 mother solution Substances 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- LLSKXGRDUPMXLC-UHFFFAOYSA-N 1-phenylpiperidine Chemical class C1CCCCN1C1=CC=CC=C1 LLSKXGRDUPMXLC-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 210000003568 synaptosome Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention relates to a purification method of paroxetine hydrochloride, which comprises (a) adding solvent and acid into paroxetine hydrochloride, heating and stirring until the solution is clear; (b) Optionally adding a proper amount of activated carbon, and stirring for a certain time at a constant temperature; (c) filtering, cooling and crystallizing; (d) And after crystallization, separating and drying to obtain pure paroxetine hydrochloride. The purification method of paroxetine hydrochloride provided by the invention is simple to operate, the raw materials are cheap, the conditions are mild, and the obtained pure paroxetine hydrochloride does not turn red.
Description
The present application claims priority from the chinese patent office, filed on 12 months 10 in 2020, under the name 202011083040.9, entitled "method for preparing paroxetine hcl", the entire contents of which are incorporated herein by reference.
The invention relates to a purification method of paroxetine hydrochloride, belonging to the field of pharmaceutical chemistry.
Paroxetine hydrochloride, the structural formula of which is shown in formula I. Paroxetine hydrochloride is a phenylpiperidine derivative, can strongly and selectively inhibit reuptake of 5-hydroxytryptamine of neuron synaptosomes, enables 5-hydroxytryptamine among neuron synapses to accumulate, promotes 5-hydroxytryptamine to transfer, plays an antidepressant role, has weaker effect on other transmitters, has smaller influence on a vegetative nervous system and a cardiovascular system, and belongs to a serotonin reuptake inhibitor (SSRI) drug.
Paroxetine hydrochloride presents a general technical problem in that color changes (pink) may occur during production or storage of Paroxetine hydrochloride APIs. Chinese patent application CN1516585a suggests that one impurity in paroxetine hydrochloride plays a role in color change to pink, the Relative Retention Time (RRT) of this impurity in High Pressure Liquid Chromatography (HPLC) is about 1.5, however at lower levels of this impurity a color change can still occur, revealing that other impurities may also play a role in color change.
The present inventors have found that there is a certain probability of obtaining a pink paroxetine product during the existing paroxetine production process, and that conventional purification methods are difficult to remove the pink product and require multiple purifications to convert the pink product to a white product. Therefore, it is necessary to develop a method for stably purifying paroxetine HCl in white.
Disclosure of Invention
The present invention provides a process for purifying paroxetine hcl comprising the steps of:
(a) Adding a solvent and an acid into the paroxetine hydrochloride crude product, heating and stirring until the paroxetine hydrochloride crude product is dissolved and clarified;
(b) Optionally adding a proper amount of activated carbon, and stirring for a certain time at a constant temperature;
(c) Filtering, cooling and crystallizing;
(d) And after crystallization, separating and drying to obtain a finished product of paroxetine hydrochloride.
As a preferred embodiment of the present invention:
wherein the solvent in the step (a) is a single organic solvent or a mixed solution prepared by organic solvent and water. Wherein the organic solvent is water-miscible organic solvent, preferably methanol, ethanol or acetone.
The mass ratio of the volume of the solvent to the paroxetine hydrochloride is 5mL/g to 50mL/g.
Wherein the acid in step (a) is an inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid, etc., preferably hydrochloric acid. The molar ratio of acid to paroxetine HCl is from 0.016 to 0.16, preferably 0.032.
The temperature is raised in step (a) to 50℃to 90℃and preferably 55℃to 80 ℃.
The temperature in step (c) is reduced to-10℃to 5℃and preferably-5℃to 0 ℃.
The purification method also comprises the steps of adding a proper amount of solvent after filtering in the step (c), and cooling and crystallizing. The solvent is an organic solvent which is miscible with water, such as methanol, ethanol, acetone, etc., preferably acetone. The mass ratio of the volume of the solvent to the paroxetine hydrochloride is 5mL/g to 50mL/g.
The method described above, when activated carbon is added, the amount of activated carbon is 5% to 20% by mass of paroxetine hydrochloride.
The purification method of paroxetine hydrochloride provided by the invention has the advantages that:
(1) The product obtained by the purification method of paroxetine hydrochloride is white, has high purity and does not turn red;
(2) The purification method of paroxetine hydrochloride has the advantages of mild reaction conditions, high safety, simple operation process and easy industrialized production;
(3) The method for purifying paroxetine hydrochloride has low raw material cost, no toxicity and no harm;
(4) The purification method of paroxetine hydrochloride is suitable for mother liquor recovery, and is beneficial to reducing the cost.
The present invention will be further described in detail with reference to the following examples, in order to make the objects, technical solutions, and advantages of the present invention more apparent. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention are within the scope of the present invention.
In order to show the purification effect of the invention, the raw materials adopted in the experimental process of the invention are all pink paroxetine hydrochloride. The preparation process of the raw materials comprises the following steps: and (3) taking the refined mother liquor of paroxetine hydrochloride, concentrating to dryness to obtain paroxetine hydrochloride, adding acetone with the volume/mass ratio of 5mL/g to paroxetine hydrochloride, heating to 55-60 ℃, introducing oxygen, stirring until the solution turns pink, adding acetone with the volume/mass ratio to paroxetine hydrochloride, slowly cooling to-5-0 ℃, preserving heat, stirring for 2-4 hours, centrifuging, filtering, and drying to obtain the pink paroxetine hydrochloride. Yield 70%, purity: 99.27%.
Example 1
The method comprises the steps of sequentially adding 12.5g of pink paroxetine hydrochloride, 62.5mL of acetone and 0.1mL of refined hydrochloric acid into a three-port bottle, heating to 55-60 ℃, slowly dripping purified water until the mixture is stirred, dissolved and clarified (the purified water consumption is about 4.4 mL), filtering, adding 62.5mL of acetone into filtrate, slowly cooling to-5-0 ℃, preserving heat, stirring for 2-4 hours, centrifuging, filtering, and drying to obtain paroxetine hydrochloride. Yield: 85%, purity: 99.87%. Color: white crystalline powder.
Example 2
The method comprises the steps of sequentially adding 12.5g of pink paroxetine hydrochloride, 62.5mL of acetone and 0.5mL of refined hydrochloric acid into a three-port bottle, heating to 55-60 ℃, slowly dripping purified water until the mixture is stirred, dissolved and clarified (the purified water consumption is about 4.4 mL), filtering, adding 62.5mL of acetone into the filtrate, slowly cooling to-5-0 ℃, preserving heat, stirring for 2-4 hours, centrifuging, filtering, and drying to obtain paroxetine hydrochloride. Yield: 83%, purity: 99.89%. Color: white crystalline powder.
Example 3
The method comprises the steps of sequentially adding 12.5g of pink paroxetine hydrochloride, 62.5mL of methanol and 0.05mL of refined hydrochloric acid into a three-mouth bottle, heating to 60-65 ℃, stirring, dissolving, clarifying, filtering, slowly cooling to-5-0 ℃, preserving heat, stirring for 2-4 hours, centrifuging, filtering, and drying to obtain paroxetine hydrochloride. Yield: 80%, purity: 99.93%. Color: white crystalline powder.
Example 4
The method comprises the steps of sequentially adding 12.5g of pink paroxetine hydrochloride, 62.5mL of ethanol and 0.1mL of refined hydrochloric acid into a three-mouth bottle, heating to 75-80 ℃, stirring, dissolving, clarifying, filtering, slowly cooling to-5-0 ℃, preserving heat, stirring for 2-4 hours, centrifuging, filtering, and drying to obtain paroxetine hydrochloride. Yield: 82%, purity: 99.92%. Color: white crystalline powder.
Example 5
The method comprises the steps of sequentially adding 12.5g of pink paroxetine hydrochloride, 625mL of acetone and 0.1mL of refined hydrochloric acid into a three-mouth bottle, heating to 55-60 ℃, filtering, slowly cooling to-5-0 ℃, preserving heat, stirring for 2-4 hours, centrifuging, filtering and drying to obtain paroxetine hydrochloride. Yield: 75%, purity: 99.91%. Color: white crystalline powder.
Example 6
500mL of a purified paroxetine HCl mother solution (the filtrate obtained after centrifugal filtration by the same purification method as in example 1) was sequentially added to a three-necked flask, the temperature was controlled at 40℃to 60℃and the mixture was concentrated to dryness under reduced pressure to obtain 10g of a crude recovered product. 50mL of acetone and 0.1mL of refined hydrochloric acid are added, the temperature is raised to 55 ℃ to 50 ℃, 2.6mL of purified water is added dropwise, and the mixture is stirred, dissolved and clarified. Adding 1g of active carbon, stirring for 1 hour under heat preservation, filtering, and taking filtrate. And adding 50mL of acetone into the filtrate, slowly cooling to 35+/-5 ℃, cooling to-5 ℃ to 0 ℃, maintaining the temperature, stirring for 1 hour, filtering, and drying a filter cake to obtain 8.1g (white crystalline powder) of recovered paroxetine hydrochloride, wherein the recovery rate is 81% (the recovery rate=the yield/the crude recovery rate is 100%), and the purity is 99.88%.
Example 7
500mL of a purified paroxetine HCl mother solution (the filtrate obtained after centrifugal filtration by the same purification method as in example 1) was sequentially added to a three-necked flask, the temperature was controlled at 40℃to 60℃and the mixture was concentrated to dryness under reduced pressure to obtain 10g of a crude recovered product. 50mL of acetone and 0.2mL of refined hydrochloric acid are added, the temperature is raised to 55 ℃ to 50 ℃, 2.5mL of purified water is added dropwise, and the mixture is stirred, dissolved and clarified. 2g of active carbon is added, the mixture is stirred for 1 hour under heat preservation, and the filtrate is filtered. And adding 50mL of acetone into the filtrate, slowly cooling to 35+/-5 ℃, cooling to-5 ℃ to 0 ℃, maintaining the temperature, stirring for 1 hour, filtering, and drying a filter cake to obtain 8.0g (white crystalline powder) of recovered paroxetine hydrochloride, wherein the recovery rate is 80% (the recovery rate=the yield/the crude recovery rate is 100%), and the purity is 99.84%.
Comparative example 1:
sequentially adding 12.5g of pink paroxetine hydrochloride and 62.5mL of acetone into a three-mouth bottle, heating to 55-60 ℃, slowly dripping purified water until stirring and dissolving (the consumption of the purified water is about 4.4 mL), filtering, adding 62.5mL of acetone into the filtrate, slowly cooling to-5-0 ℃, preserving heat and stirring for 2-4 hours, centrifuging, filtering, and drying to obtain paroxetine hydrochloride. Yield: 86%, purity: 99.8%. Color: pink crystalline powder.
Example 8:
stability investigation: with reference to the samples obtained in examples 1 to 7, the white color remained after storage observation at room temperature of 20 ℃ to 30 ℃ for 1 year, purity: 99.8% or more.
The foregoing description of the preferred embodiments of the invention is not intended to limit the invention to the precise form disclosed, and any such modifications, equivalents, and alternatives falling within the spirit and scope of the invention are intended to be included within the scope of the invention.
Claims (11)
- A process for purifying paroxetine hcl, the process comprising the steps of:(a) Adding a solvent and an acid into paroxetine hydrochloride, heating and stirring until the paroxetine hydrochloride is dissolved and clarified;(b) Optionally adding a proper amount of activated carbon, and stirring for a certain time at a constant temperature;(c) Filtering, cooling and crystallizing;(d) After crystallization, separating and drying to obtain pure paroxetine hydrochloride,wherein the molar ratio of acid to paroxetine HCl in step (a) is from 0.016 to 0.16, preferably 0.032.
- The method of claim 1, wherein the solvent in step (a) is a single organic solvent or a mixed solution of an organic solvent and water.
- The process according to claim 2, wherein the organic solvent is a water miscible organic solvent, preferably methanol, ethanol or acetone.
- The process according to claim 1 or 2, wherein the mass ratio of the volume of the solvent to paroxetine hcl is from 5mL/g to 50mL/g.
- The process according to any one of claims 1 to 4, wherein the acid in step (a) is a mineral acid, preferably hydrochloric acid, sulfuric acid or nitric acid.
- The process according to any one of claims 1 to 5, wherein in step (a) the temperature is raised to 50 ℃ to 90 ℃, preferably 55 ℃ to 80 ℃.
- The method of any one of claims 1 to 6, further comprising adding an appropriate amount of solvent after filtering in step (c), and cooling to crystallize.
- The method according to claim 7, wherein the additional solvent is a water miscible organic solvent, preferably methanol, ethanol or acetone.
- The process of claim 7, wherein the mass ratio of the volume of the additional solvent to paroxetine hcl is from 5mL/g to 50mL/g.
- The process according to any one of claims 1 to 9, when activated carbon is added, the mass of activated carbon is 5% to 20% of the mass of paroxetine hcl.
- The process according to any one of claims 1 to 10, wherein in step (c) the temperature is reduced to-10 ℃ to 5 ℃, preferably-5 ℃ to 0 ℃.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011083040.9A CN112159398A (en) | 2020-10-12 | 2020-10-12 | Preparation method of paroxetine hydrochloride |
| CN2020110830409 | 2020-10-12 | ||
| PCT/CN2021/123203 WO2022078312A1 (en) | 2020-10-12 | 2021-10-12 | Method for purifying paroxetine hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116348110A true CN116348110A (en) | 2023-06-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011083040.9A Pending CN112159398A (en) | 2020-10-12 | 2020-10-12 | Preparation method of paroxetine hydrochloride |
| CN202180066909.5A Pending CN116348110A (en) | 2020-10-12 | 2021-10-12 | Paroxetine hydrochloride purification method |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011083040.9A Pending CN112159398A (en) | 2020-10-12 | 2020-10-12 | Preparation method of paroxetine hydrochloride |
Country Status (2)
| Country | Link |
|---|---|
| CN (2) | CN112159398A (en) |
| WO (1) | WO2022078312A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112159398A (en) * | 2020-10-12 | 2021-01-01 | 浙江华海药业股份有限公司 | Preparation method of paroxetine hydrochloride |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1295572A (en) * | 1998-02-06 | 2001-05-16 | 史密丝克莱恩比彻姆有限公司 | Salt of paroxetine |
| IL159280A0 (en) * | 2001-06-14 | 2004-06-01 | Teva Pharma | A process for preparing paroxetine hcl which limits formation of pink colored compounds |
| CN102285973B (en) * | 2011-09-20 | 2013-03-06 | 海南美大制药有限公司 | Paroxetine hydrochloride compound and preparation method thereof |
| CN112159398A (en) * | 2020-10-12 | 2021-01-01 | 浙江华海药业股份有限公司 | Preparation method of paroxetine hydrochloride |
-
2020
- 2020-10-12 CN CN202011083040.9A patent/CN112159398A/en active Pending
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2021
- 2021-10-12 CN CN202180066909.5A patent/CN116348110A/en active Pending
- 2021-10-12 WO PCT/CN2021/123203 patent/WO2022078312A1/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| CN112159398A (en) | 2021-01-01 |
| WO2022078312A1 (en) | 2022-04-21 |
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