CA2316991A1 - Purification du tramadol - Google Patents
Purification du tramadol Download PDFInfo
- Publication number
- CA2316991A1 CA2316991A1 CA002316991A CA2316991A CA2316991A1 CA 2316991 A1 CA2316991 A1 CA 2316991A1 CA 002316991 A CA002316991 A CA 002316991A CA 2316991 A CA2316991 A CA 2316991A CA 2316991 A1 CA2316991 A1 CA 2316991A1
- Authority
- CA
- Canada
- Prior art keywords
- tramadol
- preparation
- salt
- crude
- hydrochloride
- 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.)
- Abandoned
Links
- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 title claims abstract description 62
- 229960004380 tramadol Drugs 0.000 title claims abstract description 62
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 title claims abstract description 62
- 238000000746 purification Methods 0.000 title description 7
- 238000000034 method Methods 0.000 claims abstract description 50
- 238000002360 preparation method Methods 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000001953 recrystallisation Methods 0.000 claims abstract description 17
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims abstract description 13
- PPKXEPBICJTCRU-XMZRARIVSA-N (R,R)-tramadol hydrochloride Chemical compound Cl.COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 PPKXEPBICJTCRU-XMZRARIVSA-N 0.000 claims abstract description 12
- 229960003107 tramadol hydrochloride Drugs 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 238000003747 Grignard reaction Methods 0.000 claims abstract description 9
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- QDHLEFBSGUGHCL-UHFFFAOYSA-N 2-[(dimethylamino)methyl]cyclohexan-1-one Chemical compound CN(C)CC1CCCCC1=O QDHLEFBSGUGHCL-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 5
- 239000002585 base Substances 0.000 claims description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 239000000047 product Substances 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 239000012458 free base Substances 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 208000005156 Dehydration Diseases 0.000 description 4
- 230000018044 dehydration Effects 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- 150000008378 aryl ethers Chemical class 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- TVYLLZQTGLZFBW-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol Chemical class COC1=CC=CC(C2(O)C(CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 239000003874 central nervous system depressant Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 239000013056 hazardous product Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- FKUUDDGRDRPAQQ-UHFFFAOYSA-M magnesium;methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=C[C-]=C1 FKUUDDGRDRPAQQ-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 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
- 230000017074 necrotic cell death Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000037384 skin absorption Effects 0.000 description 1
- 231100000274 skin absorption Toxicity 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
L'invention concerne un procédé pour la purification du tramadol selon une réaction de Grignard entre du 2-(diméthylaminométhyl)cyclo-hexanone et le réactif 3-méthoxyphénylMgX, où X est un halogène, de manière à obtenir la base brute destinée à être introduite dans un solvant. On met en contact ladite base avec un acide bromhydrique ou iodhydrique pour former un sel correspondant. Ensuite, on soumet ledit sel à une phase de recristallisation donnant respectivement un bromhydrate de tramadol ou un iodhydrate de tramadol, produits à partir desquels il est possible d'obtenir une base de tramadol purifiée aux fins de conversion éventuelle sous forme de produit pharmaceutique préféré (par exemple, chlorhydrate de tramadol).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9800656.2A GB9800656D0 (en) | 1998-01-14 | 1998-01-14 | Improved purification process |
| GB9800656.2 | 1998-01-14 | ||
| PCT/GB1999/000013 WO1999036390A1 (fr) | 1998-01-14 | 1999-01-14 | Purification du tramadol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2316991A1 true CA2316991A1 (fr) | 1999-07-22 |
Family
ID=10825209
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002316991A Abandoned CA2316991A1 (fr) | 1998-01-14 | 1999-01-14 | Purification du tramadol |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1047662A1 (fr) |
| KR (1) | KR20010034010A (fr) |
| AU (1) | AU744938B2 (fr) |
| CA (1) | CA2316991A1 (fr) |
| GB (1) | GB9800656D0 (fr) |
| HU (1) | HUP0100356A3 (fr) |
| IL (1) | IL136957A0 (fr) |
| NZ (1) | NZ505129A (fr) |
| PL (1) | PL341712A1 (fr) |
| SK (1) | SK10352000A3 (fr) |
| TR (1) | TR200002022T2 (fr) |
| WO (1) | WO1999036390A1 (fr) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100342919B1 (ko) * | 1999-10-21 | 2002-07-04 | 박노중 | 트랜스체 염산 트라마돌의 분리 제조방법 |
| US6649783B2 (en) | 2001-10-03 | 2003-11-18 | Euro-Celtique, S.A. | Synthesis of (+/-)-2-((dimethylamino)methyl)-1-(aryl)cyclohexanols |
| EP1346978A1 (fr) * | 2002-03-21 | 2003-09-24 | Jubilant Organosys Limited | Procédé pour la préparation de tramadol chlorohydrate et/ou de tramadol monohydrate |
| DE10236510A1 (de) * | 2002-08-09 | 2004-02-19 | Grünenthal GmbH | Verfahren zur Herstellung von 2-[(Dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol |
| EP1785412A1 (fr) | 2005-11-14 | 2007-05-16 | IPCA Laboratories Limited | Procédé de récuperation de Tramadol |
| WO2010032254A1 (fr) * | 2008-09-22 | 2010-03-25 | Kamud Drugs Pvt . Ltd . | Procédé industriel pour la préparation de cis(+m-2-r(diméthylamino)-méthyl-1-(3- méthoxyphényl) cyclohexanol chlorhydrate |
| WO2014154747A1 (fr) | 2013-03-26 | 2014-10-02 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Extraction de tramadol à partir de nauclea latifolia smith |
| USD828429S1 (en) | 2015-02-23 | 2018-09-11 | Samsung Electronics Co., Ltd. | Digital camera |
| US20210317086A1 (en) * | 2018-08-20 | 2021-10-14 | Mylan Laboratories Limited | Tramadol HBR-Celecoxib Co-Crystal |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3652589A (en) * | 1967-07-27 | 1972-03-28 | Gruenenthal Chemie | 1-(m-substituted phenyl)-2-aminomethyl cyclohexanols |
| IL103096A (en) * | 1992-09-08 | 1996-12-05 | Chemagis Ltd | Process for purification 2 -]) Dimethylamino (methyl-1-) 3-methoxycinyl (cyclohexanol and its salts. |
| US5877351A (en) * | 1997-12-24 | 1999-03-02 | Wyckoff Chemical Company, Inc. | Preparation and purification process for 2- (dimethylamino) methyl!-1-(3-methoxphenyl)-cyclohexanol and its salts |
-
1998
- 1998-01-14 GB GBGB9800656.2A patent/GB9800656D0/en not_active Ceased
-
1999
- 1999-01-14 TR TR2000/02022T patent/TR200002022T2/xx unknown
- 1999-01-14 SK SK1035-2000A patent/SK10352000A3/sk unknown
- 1999-01-14 PL PL99341712A patent/PL341712A1/xx unknown
- 1999-01-14 NZ NZ505129A patent/NZ505129A/en unknown
- 1999-01-14 IL IL13695799A patent/IL136957A0/xx unknown
- 1999-01-14 EP EP99901000A patent/EP1047662A1/fr not_active Withdrawn
- 1999-01-14 KR KR1020007007604A patent/KR20010034010A/ko not_active Ceased
- 1999-01-14 AU AU20637/99A patent/AU744938B2/en not_active Ceased
- 1999-01-14 HU HU0100356A patent/HUP0100356A3/hu unknown
- 1999-01-14 CA CA002316991A patent/CA2316991A1/fr not_active Abandoned
- 1999-01-14 WO PCT/GB1999/000013 patent/WO1999036390A1/fr not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| NZ505129A (en) | 2001-11-30 |
| AU744938B2 (en) | 2002-03-07 |
| HUP0100356A2 (hu) | 2002-05-29 |
| GB9800656D0 (en) | 1998-03-11 |
| TR200002022T2 (tr) | 2000-11-21 |
| EP1047662A1 (fr) | 2000-11-02 |
| AU2063799A (en) | 1999-08-02 |
| PL341712A1 (en) | 2001-04-23 |
| KR20010034010A (ko) | 2001-04-25 |
| SK10352000A3 (sk) | 2001-02-12 |
| IL136957A0 (en) | 2001-06-14 |
| HUP0100356A3 (en) | 2002-08-28 |
| WO1999036390A1 (fr) | 1999-07-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5343925B2 (ja) | （２ｒ）−２−プロピルオクタン酸の製造方法 | |
| JP2000517288A (ja) | Ｏ，ｏ’―ビスアロイル酒石酸類によるメチルフェニデートの光学分割 | |
| AU744938B2 (en) | Purification of tramadol | |
| JPWO2000048982A1 (ja) | （２ｒ）−２−プロピルオクタン酸の製造方法 | |
| JP3110459B2 (ja) | ｐ−アミノフェノール組成物の精製及びＮ−アセチル−ｐ−アミノフェノールへの直接転化 | |
| WO2020255059A1 (fr) | Procédé de purification de carfilzomib | |
| US20040259939A1 (en) | Process for the production of citalopram | |
| WO1999036389A1 (fr) | Purification du tramadol | |
| JP5220026B2 (ja) | アルファ−ケトアミドの亜硫酸水素塩精製 | |
| JPS63190840A (ja) | ソラネソ−ルの精製方法 | |
| CA2537804A1 (fr) | Procede de recyclage pour l'elaboration de sertraline | |
| JP2595554B2 (ja) | インドール類の精製方法 | |
| JP3382297B2 (ja) | 高純度デフェロキサミン塩の製造法 | |
| FR2583419A1 (fr) | Procede pour la preparation de 2-bromo-a-ergocryptine et ses sels d'addition d'acides. | |
| EA012420B1 (ru) | Улучшенный способ очистки периндоприла | |
| KR102723759B1 (ko) | 아픽사반의 제조방법 | |
| JPH0374384A (ja) | ３ｒ‐（３‐カルボキシベンジル）‐６‐（５‐フルオロ‐２‐ベンゾチアゾリル）メトキシ‐４ｒ‐クロマノールの光学分割方法 | |
| JP6894945B2 (ja) | ルビプロストン結晶およびその調製方法 | |
| JPH01135732A (ja) | 分離方法 | |
| WO2024140870A1 (fr) | Procédé de séparation d'un intermédiaire de ramipril | |
| CN121064021A (zh) | 一种制备盐酸去氧肾上腺素基因毒性杂质的方法 | |
| SU1198065A1 (ru) | Способ получени бензойного эфира @ -изомера 2,5-диметилпиперидола- @ | |
| CN114478347A (zh) | 一种维纳卡兰中间体的精制方法 | |
| JPH0770070A (ja) | 光学活性な１−（４−クロロピリジン−２−イル）−２−（ピリジン−２−イル）エチルアミンの製造法および中間体 | |
| FR2552767A1 (fr) | Procede de preparation de la digoxine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |