TWI221473B - Process for the production of paroxetine - Google Patents
Process for the production of paroxetine Download PDFInfo
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- TWI221473B TWI221473B TW089102997A TW89102997A TWI221473B TW I221473 B TWI221473 B TW I221473B TW 089102997 A TW089102997 A TW 089102997A TW 89102997 A TW89102997 A TW 89102997A TW I221473 B TWI221473 B TW I221473B
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- 238000000034 method Methods 0.000 title claims abstract description 34
- 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 title abstract description 5
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 title abstract description 5
- 229960002296 paroxetine Drugs 0.000 title abstract description 5
- 230000008569 process Effects 0.000 title abstract description 4
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- 239000003446 ligand Substances 0.000 claims abstract description 17
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 16
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 13
- 150000003624 transition metals Chemical class 0.000 claims abstract description 13
- LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Natural products OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 42
- 150000001875 compounds Chemical class 0.000 claims description 40
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 30
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 28
- 238000011049 filling Methods 0.000 claims description 24
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 claims description 20
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- 239000002904 solvent Substances 0.000 claims description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 claims description 14
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- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 3
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- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 claims description 2
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- PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 claims 2
- 239000012327 Ruthenium complex Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims 1
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- KCTLGSREBLDQRJ-UHFFFAOYSA-N benzenesulfonamide;methane Chemical compound C.NS(=O)(=O)C1=CC=CC=C1 KCTLGSREBLDQRJ-UHFFFAOYSA-N 0.000 claims 1
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 1
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- 238000011065 in-situ storage Methods 0.000 claims 1
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- 230000015572 biosynthetic process Effects 0.000 abstract description 13
- 230000000707 stereoselective effect Effects 0.000 abstract description 4
- UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 abstract description 2
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- 239000002184 metal Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 210000002268 wool 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT1999MI000364A IT1308629B1 (it) | 1999-02-23 | 1999-02-23 | Processo per la produzione di paroxetina. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TWI221473B true TWI221473B (en) | 2004-10-01 |
Family
ID=11382007
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW089102997A TWI221473B (en) | 1999-02-23 | 2000-02-18 | Process for the production of paroxetine |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US6583287B1 (https=) |
| EP (1) | EP1153023B1 (https=) |
| JP (1) | JP2002537394A (https=) |
| KR (1) | KR20010102366A (https=) |
| CN (1) | CN1161353C (https=) |
| AT (1) | ATE238295T1 (https=) |
| AU (1) | AU759441B2 (https=) |
| BR (1) | BR0008220A (https=) |
| CA (1) | CA2361758A1 (https=) |
| CZ (1) | CZ20012997A3 (https=) |
| DE (1) | DE60002303T2 (https=) |
| DK (1) | DK1153023T3 (https=) |
| ES (1) | ES2195876T3 (https=) |
| HK (1) | HK1040516B (https=) |
| HR (1) | HRP20010608A2 (https=) |
| HU (1) | HUP0105482A3 (https=) |
| IL (1) | IL144883A (https=) |
| IT (1) | IT1308629B1 (https=) |
| MX (1) | MXPA01008502A (https=) |
| NO (1) | NO319724B1 (https=) |
| PL (1) | PL349358A1 (https=) |
| PT (1) | PT1153023E (https=) |
| RU (1) | RU2242473C2 (https=) |
| SK (1) | SK12042001A3 (https=) |
| TR (1) | TR200102441T2 (https=) |
| TW (1) | TWI221473B (https=) |
| WO (1) | WO2000050422A1 (https=) |
| YU (1) | YU60801A (https=) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE602005001873T2 (de) * | 2004-03-03 | 2008-04-24 | Chemi S.P.A., Cinisello Balsamo | Amorphe 3-Pyridyl-1-Hydroxyethyliden-1,1-Bisphosphonsäure Mononatriumsalz und Verfahren zu deren Herstellung |
| US9138430B2 (en) * | 2007-12-27 | 2015-09-22 | Mylan Specialty L.P. | Formulation and method for the release of paroxetine in the large intestine |
| ES2576082T3 (es) * | 2012-01-31 | 2016-07-05 | Eisai R&D Management Co., Ltd. | Derivado de paroxetina |
| CN106831736A (zh) * | 2017-02-15 | 2017-06-13 | 浙江华海药业股份有限公司 | 一种制备帕罗西汀杂质的方法 |
| CN112521377A (zh) * | 2020-11-26 | 2021-03-19 | 北京福元医药股份有限公司 | 一种盐酸帕罗西汀的连续化制备方法 |
| CN115260153B (zh) * | 2022-07-21 | 2023-10-27 | 威尚（上海）生物医药有限公司 | 一种6取代手性纯二氟哌啶喹唑啉衍生物及其制备方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0757758B2 (ja) | 1988-10-24 | 1995-06-21 | 高砂香料工業株式会社 | ルテニウム―ホスフィン錯体 |
| DK715988D0 (da) * | 1988-12-22 | 1988-12-22 | Ferrosan As | Etherifikation og dealkylering af piperidin-derivater samt intermediater |
| US5233084A (en) | 1989-06-22 | 1993-08-03 | Monsanto Company | Method for preparing α-arylpropionic acids |
| FR2651152B1 (fr) * | 1989-08-23 | 1991-11-29 | Elf Aquitaine | Perfectionnement a la preparation de catalyseurs chiraux a base de complexes du ruthenium et du phosphore. |
| GB9209687D0 (en) | 1992-05-06 | 1992-06-17 | Smithkline Beecham Plc | Novel process |
| DE4422672A1 (de) * | 1994-06-30 | 1996-01-04 | Hoechst Ag | Halogenierte Biphenyl-2,2'-diyl-bis-diphenylphosphine, ihre Herstellung und ihre Verwendung |
| SK283608B6 (sk) * | 1995-02-06 | 2003-10-07 | Smithkline Beecham Plc | Bezvodý hydrochlorid paroxetínu, spôsob jeho výroby a použitie |
| HUP9900318A3 (en) * | 1995-05-17 | 2001-09-28 | Novo Nordisk As | Process for preparing 4-aryl-piperidine derivatives |
| HU221921B1 (hu) * | 1996-07-08 | 2003-02-28 | Richter Gedeon Vegyészeti Gyár Rt. | N-benzil-piperidin- és tetrahidropiridinszármazékok és eljárás azok előállítására |
| IL132170A0 (en) * | 1997-05-06 | 2001-03-19 | Novo Nordisk As | Novel heterocyclic compounds |
| DE69820205T2 (de) * | 1997-05-20 | 2004-09-30 | Firmenich S.A. | Ruthenium-katalysatoren und ihre verwendung zur asymmetrischen hydrierung von substraten mit schwacher koordination |
-
1999
- 1999-02-23 IT IT1999MI000364A patent/IT1308629B1/it active
-
2000
- 2000-02-18 TW TW089102997A patent/TWI221473B/zh not_active IP Right Cessation
- 2000-02-22 EP EP00909228A patent/EP1153023B1/en not_active Expired - Lifetime
- 2000-02-22 US US09/890,414 patent/US6583287B1/en not_active Expired - Fee Related
- 2000-02-22 JP JP2000601002A patent/JP2002537394A/ja active Pending
- 2000-02-22 AT AT00909228T patent/ATE238295T1/de not_active IP Right Cessation
- 2000-02-22 CZ CZ20012997A patent/CZ20012997A3/cs unknown
- 2000-02-22 CN CNB008041873A patent/CN1161353C/zh not_active Expired - Fee Related
- 2000-02-22 BR BR0008220-1A patent/BR0008220A/pt not_active IP Right Cessation
- 2000-02-22 PT PT00909228T patent/PT1153023E/pt unknown
- 2000-02-22 DK DK00909228T patent/DK1153023T3/da active
- 2000-02-22 IL IL14488300A patent/IL144883A/en not_active IP Right Cessation
- 2000-02-22 HK HK02101971.9A patent/HK1040516B/en not_active IP Right Cessation
- 2000-02-22 PL PL00349358A patent/PL349358A1/xx not_active IP Right Cessation
- 2000-02-22 DE DE60002303T patent/DE60002303T2/de not_active Expired - Fee Related
- 2000-02-22 MX MXPA01008502A patent/MXPA01008502A/es active IP Right Grant
- 2000-02-22 WO PCT/EP2000/001430 patent/WO2000050422A1/en not_active Ceased
- 2000-02-22 SK SK1204-2001A patent/SK12042001A3/sk unknown
- 2000-02-22 TR TR2001/02441T patent/TR200102441T2/xx unknown
- 2000-02-22 AU AU31583/00A patent/AU759441B2/en not_active Ceased
- 2000-02-22 HU HU0105482A patent/HUP0105482A3/hu unknown
- 2000-02-22 HR HR20010608A patent/HRP20010608A2/hr not_active Application Discontinuation
- 2000-02-22 RU RU2001125933/04A patent/RU2242473C2/ru not_active IP Right Cessation
- 2000-02-22 CA CA002361758A patent/CA2361758A1/en not_active Abandoned
- 2000-02-22 ES ES00909228T patent/ES2195876T3/es not_active Expired - Lifetime
- 2000-02-22 KR KR1020017010760A patent/KR20010102366A/ko not_active Ceased
- 2000-02-22 YU YU60801A patent/YU60801A/sh unknown
-
2001
- 2001-08-22 NO NO20014078A patent/NO319724B1/no unknown
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