US20090018365A1 - Methods for Preparing O-Desmethylvenlafaxine - Google Patents
Methods for Preparing O-Desmethylvenlafaxine Download PDFInfo
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- US20090018365A1 US20090018365A1 US12/208,990 US20899008A US2009018365A1 US 20090018365 A1 US20090018365 A1 US 20090018365A1 US 20899008 A US20899008 A US 20899008A US 2009018365 A1 US2009018365 A1 US 2009018365A1
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- Prior art keywords
- desmethylvenlafaxine
- thiolate anion
- reaction
- venlafaxine
- carbon atoms
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- PZSHCGSAQAAGCU-UHFFFAOYSA-N CN(C)CC(C1=CC=C(O)C=C1)C1(O)CCCCC1.COC1=CC=C(C(CN(C)C)C2(O)CCCCC2)C=C1 Chemical compound CN(C)CC(C1=CC=C(O)C=C1)C1(O)CCCCC1.COC1=CC=C(C(CN(C)C)C2(O)CCCCC2)C=C1 PZSHCGSAQAAGCU-UHFFFAOYSA-N 0.000 description 1
Classifications
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- 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
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
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- 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
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- 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
- A61P25/06—Antimigraine agents
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- 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
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- 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
Definitions
- O-desmethylvenlafaxine is a major metabolite of venlafaxine. Methods to make O-desmethylvenlafaxine are described in U.S. Pat. No. 4,535,186. This method uses benzyl blocking groups leading to relatively low throughput.
- a process of making O-desmethylvenlafaxine is also described in WO 00/59851 in which venlafaxine is allowed to react with diphenyl phosphide in THF (generated by adding n-butyl lithium in THF to diphenylphosphine in THF below 0° C.) at reflux for an overnight period.
- the yield was reported to be 73.8%.
- the method involved extraction steps involving large volumes of solvent.
- the present invention provides a process of making O-desmethylvenlafaxine which is both time and material efficient.
- Venlafaxine As described in Scheme I the starting material, venlafaxine (Formula I), is demethylated. Venlafaxine may be prepared in accordance with procedures known in the art such as described in U.S. Pat. No. 4,535,186.
- demethylation is performed using a high molecular weight alkane, arene, or arylalkyl thiolate anion, such as straight or branched chain alkane thiolate anions having 8 to 20 carbon atoms, mono or bicyclic arene thiolate anions having 6 to 10 carbon atoms, or mono or bicyclic arylalkyl thiolate anions having 7 to 12 carbon atoms in the presence of a protic or aprotic solvent.
- a base such as an alkoxide comprised of a straight or branched chain alkyl group of from 1 to 6 carbon atoms may be present to generate the thiolate anion.
- the aliphatic thiol has from 10 to 20 carbon atoms and most preferably the aliphatic thiol is dodecanethiol.
- the aromatic thiol is preferably benzenethiol.
- the arylalkyl thiolate anion is preferably toluenethiol or naphthylmethanethiol.
- the alkoxide is preferably a lower alkoxide (methoxide, ethoxide and the like) such as sodium methoxide (sodium methylate, sodium methanolate).
- the solvent is preferably a hydroxylic or ethereal solvent, and more preferably an alcohol, ethylene glycol or ether of ethylene glycol.
- Ethers of ethylene glycol include, but are not limited to, ethylene glycol monoethyl ether, triethylene glycol dimethyl ether and polyethylene glycol.
- the solvent is an inert, polar, high boiling point ether of ethylene glycol such as polyethylene glycol and most preferably PEG 400 (polyethylene glycol having a molecular weight range of from about 380-420).
- the reaction is performed at a temperature of from about 150° C. to about 220° C., more preferably from about 170° C. to about 220° C., and most preferably from about 180° C. to about 200° C.
- the reaction is generally allowed to progress until, ideally, not more than 1% venlafaxine remains.
- the reaction is complete in from about 2 hours to about 5 hours and more preferably in from about 2 to about 3.5 hours.
- the thiolate anion can be prepared separately or in situ.
- venlafaxine base is dissolved in polyethylene glycol 400 containing dodecanethiol and sodium methylate as a solution in methanol as the temperature is increased to from about 180° C. to about 200° C., with stirring for about 2 to about 3.5 hours.
- venlafaxine base is dissolved in polyethylene glycol containing dodecanethiolate and stirred for about 2 to about 3.5 hours at from about 180° C. to about 200° C. with stirring.
- reaction mixture is cooled to between about 65° C. and about 75° C. and an alcohol may be added as a diluent before neutralization to the isoelectric point (about pH9.5 to about pH10.0) with an appropriate neutralization agent such as hydrochloric acid.
- an appropriate neutralization agent such as hydrochloric acid.
- the alcoholic medium may also aid in the crystallization of the product as neutralization is initiated.
- the alcohol comprises a straight or branched chain alkyl group of 1 to 6 carbon atoms, such as methanol, ethanol, isopropanol, butanol, and the like, and mixtures thereof.
- the alcohol is isopropanol.
- Yields of the present invention are greater than about 75% and generally from about 85% to greater than 90%.
- Dodecanethiol (122 g), venlafaxine (111 g), and a methanolic solution of sodium methanolate (30%, 90 g) and PEG 400 are heated to 190° C.
- the methanol is distilled off and the solution is stirred 2 h at 190° C.
- 2-propanol (450 g) is added and the pH is adjusted to 9.5 with aqueous HCl.
- the precipitate is collected by suction filtration, and the cake is washed with 2-propanol, toluene, 2-propanol and water.
- the wet O-desmethylvenlafaxine is dried in vacuo.
- Venlafaxine (5.6 g) and benzenethiol sodium salt (6.9 g) are charged to PEG 400 (25 g).
- the reaction mixture is heated to 160° C. for 5 h. Then the temperature is lowered and water is added (60 g).
- the pH is adjusted to 3.5 with H 3 PO 4 .
- the organic by-products are removed by extraction with heptanes (25 g).
- the pH of the aqueous layer is then adjusted to 9.5 with aqueous ammonia.
- the precipitate is collected by suction filtration, re-slurried in water (100 g), isolated by suction filtration and dried in vacuo.
- Dodecanethiol (69 g) venlafaxine (55 g) and an ethanolic solution of sodium ethanolate (21%, 82 g) are charged to a pressure vessel.
- the temperature is raised to 150° C. and the reaction mixture is stirred for 2 days.
- the temperature is lowered and the solution is filtered.
- the pH of the filtrate is adjusted to 9.5 with aqueous hydrogen chloride.
- the crystals are collected by suction filtration. The cake is washed with ethanol and dried in vacuo.
- Dodecanethiol (246 g) and sodium methylate in methanol 30% (216 g) are charged to a rotary evaporator. Vacuum is applied and the solvent is abstracted completely using a bath temperature up to 90° C. The remaining sodium dodecanethiolate (272 g) is used without further purification in the subsequent step.
- a mixture of sodium dodecanethiolate (272 g) venlafaxine (256 g) and PEG 400 (185 g) is stirred 3 h at 190° C. Then the temperature is lowered and 2-propanol (915 g) is added and the pH is adjusted to 9.5 with aqueous HCl. The precipitate is collected by suction filtration, and the cake is washed with 2-propanol and water. The wet O-desmethylvenlafaxine is dried in vacuo. Yield: 200 g.
Abstract
The present invention provides an efficient method of making O-desmethyl-venlafaxine.
Description
- This application claims priority from co-pending provisional application Ser. No. 60/334,953, filed on Dec. 4, 2001, the entire disclosure of which is hereby incorporated by reference.
- O-desmethylvenlafaxine is a major metabolite of venlafaxine. Methods to make O-desmethylvenlafaxine are described in U.S. Pat. No. 4,535,186. This method uses benzyl blocking groups leading to relatively low throughput.
- A process of making O-desmethylvenlafaxine is also described in WO 00/59851 in which venlafaxine is allowed to react with diphenyl phosphide in THF (generated by adding n-butyl lithium in THF to diphenylphosphine in THF below 0° C.) at reflux for an overnight period. The yield was reported to be 73.8%. Furthermore, the method involved extraction steps involving large volumes of solvent.
- The present invention provides a process of making O-desmethylvenlafaxine which is both time and material efficient.
- In accordance with the present invention is provided a method of making O-desmethylvenlafaxine comprising the steps of demethylating a compound of Formula I to provide a compound of Formula II as described in Scheme I.
- As described in Scheme I the starting material, venlafaxine (Formula I), is demethylated. Venlafaxine may be prepared in accordance with procedures known in the art such as described in U.S. Pat. No. 4,535,186.
- In accordance with the present invention, demethylation is performed using a high molecular weight alkane, arene, or arylalkyl thiolate anion, such as straight or branched chain alkane thiolate anions having 8 to 20 carbon atoms, mono or bicyclic arene thiolate anions having 6 to 10 carbon atoms, or mono or bicyclic arylalkyl thiolate anions having 7 to 12 carbon atoms in the presence of a protic or aprotic solvent. Optionally, a base such as an alkoxide comprised of a straight or branched chain alkyl group of from 1 to 6 carbon atoms may be present to generate the thiolate anion.
- Preferably the aliphatic thiol has from 10 to 20 carbon atoms and most preferably the aliphatic thiol is dodecanethiol. The aromatic thiol is preferably benzenethiol. The arylalkyl thiolate anion is preferably toluenethiol or naphthylmethanethiol.
- When present, the alkoxide is preferably a lower alkoxide (methoxide, ethoxide and the like) such as sodium methoxide (sodium methylate, sodium methanolate).
- The solvent is preferably a hydroxylic or ethereal solvent, and more preferably an alcohol, ethylene glycol or ether of ethylene glycol. Ethers of ethylene glycol include, but are not limited to, ethylene glycol monoethyl ether, triethylene glycol dimethyl ether and polyethylene glycol. Preferably, the solvent is an inert, polar, high boiling point ether of ethylene glycol such as polyethylene glycol and most preferably PEG 400 (polyethylene glycol having a molecular weight range of from about 380-420).
- The reaction is performed at a temperature of from about 150° C. to about 220° C., more preferably from about 170° C. to about 220° C., and most preferably from about 180° C. to about 200° C. The reaction is generally allowed to progress until, ideally, not more than 1% venlafaxine remains. In some aspects of the invention the reaction is complete in from about 2 hours to about 5 hours and more preferably in from about 2 to about 3.5 hours.
- The thiolate anion can be prepared separately or in situ. In some preferred embodiments of the present invention, venlafaxine base is dissolved in polyethylene glycol 400 containing dodecanethiol and sodium methylate as a solution in methanol as the temperature is increased to from about 180° C. to about 200° C., with stirring for about 2 to about 3.5 hours. In other preferred embodiments of the present invention, venlafaxine base is dissolved in polyethylene glycol containing dodecanethiolate and stirred for about 2 to about 3.5 hours at from about 180° C. to about 200° C. with stirring.
- Thereafter the reaction mixture is cooled to between about 65° C. and about 75° C. and an alcohol may be added as a diluent before neutralization to the isoelectric point (about pH9.5 to about pH10.0) with an appropriate neutralization agent such as hydrochloric acid. The alcoholic medium may also aid in the crystallization of the product as neutralization is initiated.
- Preferably the alcohol comprises a straight or branched chain alkyl group of 1 to 6 carbon atoms, such as methanol, ethanol, isopropanol, butanol, and the like, and mixtures thereof. In some preferred embodiments of the invention, the alcohol is isopropanol.
- Yields of the present invention are greater than about 75% and generally from about 85% to greater than 90%.
- The following Examples are illustrative but are not meant to be limiting of the present invention.
- Dodecanethiol (122 g), venlafaxine (111 g), and a methanolic solution of sodium methanolate (30%, 90 g) and PEG 400 are heated to 190° C. The methanol is distilled off and the solution is stirred 2 h at 190° C. Then the temperature is lowered, 2-propanol (450 g) is added and the pH is adjusted to 9.5 with aqueous HCl. The precipitate is collected by suction filtration, and the cake is washed with 2-propanol, toluene, 2-propanol and water. The wet O-desmethylvenlafaxine is dried in vacuo.
- Yield: 87 g.
- 1H-NMR: (Gemini 200, Varian, 200 MHz) (DMSO-d6) δ=9.11 (s, br, 1H; OH), 6.98 (d, br, J=8.4, 2H; arom.), 6.65 (d, br, J=8.4, 2H; arom.), 5.32 (s, br, 1H; OH), 3.00 (dd, J=12.3 and 8.5, 1H), 2.73 (dd, J=8.5 and 6.3, 1H), 2.36 (dd, J=12.3 and 6.3, 1H), 2.15 (s, 6H, 2×Me), 1.7-0.8 (m, 10H, c-hex).
- Venlafaxine (5.6 g) and benzenethiol sodium salt (6.9 g) are charged to PEG 400 (25 g). The reaction mixture is heated to 160° C. for 5 h. Then the temperature is lowered and water is added (60 g). The pH is adjusted to 3.5 with H3PO4. The organic by-products are removed by extraction with heptanes (25 g). The pH of the aqueous layer is then adjusted to 9.5 with aqueous ammonia. The precipitate is collected by suction filtration, re-slurried in water (100 g), isolated by suction filtration and dried in vacuo.
- Yield 1 g.
- 1H-NMR: (Gemini 200, Varian, 200 MHz) (DMSO-d6) δ=9.11 (s, br, 1H; OH), 6.98 (d, br, J=8.4, 2H; arom.), 6.65 (d, br, J=8.4, 2H; arom.), 5.32 (s, br, 1H; OH), 3.00 (dd, J=12.3 and 8.5, 1H), 2.73 (dd, J=8.5 and 6.3, 1H), 2.36 (dd, J=12.3 and 6.3, 1H), 2.15 (s, 6H, 2×Me), 1.7-0.8 (m, 10H, c-hex).
- Dodecanethiol (69 g) venlafaxine (55 g) and an ethanolic solution of sodium ethanolate (21%, 82 g) are charged to a pressure vessel. The temperature is raised to 150° C. and the reaction mixture is stirred for 2 days. Then the temperature is lowered and the solution is filtered. The pH of the filtrate is adjusted to 9.5 with aqueous hydrogen chloride. The crystals are collected by suction filtration. The cake is washed with ethanol and dried in vacuo.
- Yield: 42 g
- 1H-NMR: (Gemini 200, Varian, 200 MHz) (DMSO-d6) δ=9.11 (s, br, 1H; OH), 6.98 (d, br, J=8.4, 2H; arom.), 6.65 (d, br, J=8.4, 2H; arom.), 5.32 (s, br, 1H; OH), 3.00 (dd, J=12.3 and 8.5, 1H), 2.73 (dd, J=8.5 and 6.3, 1H), 2.36 (dd, J=12.3 and 6.3, 1H), 2.15 (s, 6H, 2×Me), 1.7-0.8 (m, 10H, c-hex).
- Dodecanethiol (246 g) and sodium methylate in methanol 30% (216 g) are charged to a rotary evaporator. Vacuum is applied and the solvent is abstracted completely using a bath temperature up to 90° C. The remaining sodium dodecanethiolate (272 g) is used without further purification in the subsequent step.
- A mixture of sodium dodecanethiolate (272 g) venlafaxine (256 g) and PEG 400 (185 g) is stirred 3 h at 190° C. Then the temperature is lowered and 2-propanol (915 g) is added and the pH is adjusted to 9.5 with aqueous HCl. The precipitate is collected by suction filtration, and the cake is washed with 2-propanol and water. The wet O-desmethylvenlafaxine is dried in vacuo. Yield: 200 g.
- 1H-NMR: (Gemini 200, Varian, 200 MHz) (DMSO-d6) δ=9.11 (s, br, 1H; OH), 6.98 (d, br, J=8.4, 2H; arom.), 6.65 (d, br, J=8.4, 2H; arom.), 5.32 (s, br, 1H; OH), 3.00 (dd, J=12.3 and 8.5, 1H), 2.73 (dd, J=8.5 and 6.3, 1H), 2.36 (dd, J=12.3 and 6.3, 1H), 2.15 (s, 6H, 2×Me), 1.7-0.8 (m, 10H, c-hex).
Claims (15)
1. A method of preparing O-desmethylvenlafaxine which comprises reacting venlafaxine with a high molecular weight alkane or arene thiolate anion in an alcohol, ethylene glycol, ether of ethylene glycol, or mixture thereof, to provide O-desmethylvenlafaxine.
2. The method of claim 1 wherein the reaction is performed at about 150° C. to about 220° C.
3. The method of claim 1 wherein the reaction is carried out for about 2 to about 5 hours.
4. The method of claim 1 wherein the thiolate anion is a straight or branched chain alkane thiolate anion having 8 to 20 carbon atoms.
5. The method of claim 1 wherein the thiol is an arene thiolate anion having from 6 to 10 carbon atoms.
6. The method of claim 4 wherein the alkane thiolate anion is dodecanethiolate.
7. The method of claim 5 wherein the arene thiolate anion is benzenethiolate.
8. The method of claim 1 wherein the thiolate anion is generated in the presence of an alkoxide.
9. The method of claim 8 wherein the alkoxide is methoxide.
10. The method of claim 2 wherein the reaction is performed at from about 170° C. to about 220° C.
11. The method of claim 2 wherein the reaction is performed at from about 180° C. to about 200° C.
12. The method of claim 1 further comprising neutralizing the product to the isoelectric point in the presence of an alcohol comprising a straight or branched chain alkyl group of from 1 to 6 carbon atoms.
13. The method of claim 12 wherein the alcohol is isopropanol.
14. The method of claim 12 wherein the isoelectric point is about pH9.5 to about pH10.
15. A method of preparing O-desmethylvenlafaxine which comprises the steps of demethylating venlafaxine with dodecyl thiolate and polyethylene glycol 400 in the presence of sodium methylate in methanol at about 180° C. to about 200° C. for about 2 to about 5 hours; and neutralizing the product to about pH 9.5 in the presence of isopropanol.
Priority Applications (1)
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US12/208,990 US20090018365A1 (en) | 2001-12-04 | 2008-09-11 | Methods for Preparing O-Desmethylvenlafaxine |
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US33495301P | 2001-12-04 | 2001-12-04 | |
US10/304,871 US6689912B2 (en) | 2001-12-04 | 2002-11-26 | Methods for preparing O-desmethylvenlafaxine |
US10/750,196 US20040158101A1 (en) | 2001-12-04 | 2003-12-31 | Methods for preparing O-desmethylvenlafaxine |
US11/756,772 US7435854B2 (en) | 2001-12-04 | 2007-06-01 | Methods for preparing O-desmethylvenlafaxine |
US12/208,990 US20090018365A1 (en) | 2001-12-04 | 2008-09-11 | Methods for Preparing O-Desmethylvenlafaxine |
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US10/304,871 Expired - Fee Related US6689912B2 (en) | 2001-12-04 | 2002-11-26 | Methods for preparing O-desmethylvenlafaxine |
US10/750,196 Abandoned US20040158101A1 (en) | 2001-12-04 | 2003-12-31 | Methods for preparing O-desmethylvenlafaxine |
US11/756,772 Expired - Fee Related US7435854B2 (en) | 2001-12-04 | 2007-06-01 | Methods for preparing O-desmethylvenlafaxine |
US12/208,990 Abandoned US20090018365A1 (en) | 2001-12-04 | 2008-09-11 | Methods for Preparing O-Desmethylvenlafaxine |
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US10/304,871 Expired - Fee Related US6689912B2 (en) | 2001-12-04 | 2002-11-26 | Methods for preparing O-desmethylvenlafaxine |
US10/750,196 Abandoned US20040158101A1 (en) | 2001-12-04 | 2003-12-31 | Methods for preparing O-desmethylvenlafaxine |
US11/756,772 Expired - Fee Related US7435854B2 (en) | 2001-12-04 | 2007-06-01 | Methods for preparing O-desmethylvenlafaxine |
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US (4) | US6689912B2 (en) |
EP (1) | EP1451143B9 (en) |
JP (1) | JP4342312B2 (en) |
KR (1) | KR100939650B1 (en) |
CN (1) | CN1319934C (en) |
AR (1) | AR037622A1 (en) |
AT (1) | ATE403641T1 (en) |
AU (1) | AU2002357049B2 (en) |
BR (1) | BR0214701A (en) |
CA (1) | CA2466779C (en) |
CO (1) | CO5580816A2 (en) |
DE (1) | DE60228118D1 (en) |
DK (1) | DK1451143T3 (en) |
EC (1) | ECSP045135A (en) |
ES (1) | ES2311647T4 (en) |
HK (1) | HK1065778A1 (en) |
HU (1) | HUP0402269A3 (en) |
IL (3) | IL162253A0 (en) |
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NO (1) | NO20042680L (en) |
NZ (1) | NZ533316A (en) |
PL (1) | PL369299A1 (en) |
PT (1) | PT1451143E (en) |
RU (1) | RU2317286C2 (en) |
SI (1) | SI1451143T1 (en) |
TW (1) | TWI260982B (en) |
UA (1) | UA80543C2 (en) |
WO (1) | WO2003048104A1 (en) |
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Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6342533B1 (en) * | 1998-12-01 | 2002-01-29 | Sepracor, Inc. | Derivatives of (−)-venlafaxine and methods of preparing and using the same |
DE60039132D1 (en) * | 1999-04-06 | 2008-07-17 | Sepracor Inc | O-desmethylvenlafaxine succinate |
PT1360169E (en) * | 2001-02-12 | 2007-10-29 | Wyeth Corp | Succinate salt of o-desmethyl-venlafaxine |
UA80543C2 (en) * | 2001-12-04 | 2007-10-10 | Wyeth Corp | Method for the preparation of o-desmethylvenlafaxine |
MX2008000249A (en) * | 2005-07-06 | 2008-03-18 | Sepracor Inc | Combinations of eszopiclone and o-desmethylvenlafaxine, and methods of treatment of menopause and mood, anxiety, and cognitive disorders. |
BRPI0619449A2 (en) * | 2005-12-05 | 2011-03-29 | Wyeth Corp | process for the stereoselective synthesis of one (4s or 4r) -4-benzyl-3- [2r or 2s] - (1-hydroxycycloexyl) - (methoxyphenyl) acetyl] -1,3-oxazolidin-2-one and one enantiomer of a 2-phenyl-2- (1-hydroxycycloalkyl) ethylamine or its salt and compounds |
EP1973866A1 (en) * | 2005-12-20 | 2008-10-01 | Synthon B.V. | Process for making desvenlafaxine |
MX2007016179A (en) * | 2006-04-17 | 2008-03-11 | Teva Pharma | Polymorphic forms of tegaserod maleate. |
EP2007708A1 (en) | 2006-04-17 | 2008-12-31 | Teva Pharmaceutical Industries Ltd | Substantially pure o-desmethylvenlafaxine and processes for preparing it |
WO2008035369A2 (en) * | 2006-06-30 | 2008-03-27 | Alembic Limited | Novel form of o-desmethyl venlafaxine |
US20090137846A1 (en) * | 2006-07-26 | 2009-05-28 | Valerie Niddam-Hildesheim | Processes for the synthesis of O-Desmethylvenlafaxine |
US20080221356A1 (en) * | 2006-07-26 | 2008-09-11 | Valerie Niddam-Hildesheim | Processes for the synthesis of O-desmethylvenlafaxine |
WO2008013995A2 (en) * | 2006-07-26 | 2008-01-31 | Teva Pharmaceutical Industries Ltd. | Tridesmethylvenlafaxine and processes for the synthesis of o-desmethylvenlafaxine |
WO2008013993A2 (en) * | 2006-07-26 | 2008-01-31 | Teva Pharmaceutical Industries Ltd. | Processes for the synthesis of o-desmethylvenlafaxine |
WO2008013994A2 (en) | 2006-07-26 | 2008-01-31 | Teva Pharmaceutical Industries Ltd. | Processes for the synthesis of o-desmethylvenlafaxine |
US20090069601A1 (en) * | 2006-07-26 | 2009-03-12 | Valerie Niddam-Hildesheim | Processes for the synthesis of O-desmethylvenlafaxine |
CA2656161A1 (en) * | 2006-07-26 | 2008-01-31 | Teva Pharmaceutical Industries Ltd. | Process for the synthesis of o-desmethylvenlafaxine |
EP2061750A2 (en) * | 2006-08-04 | 2009-05-27 | Medichem, S.A. | Improved process for synthesizing desvenlafaxine free base and salts or solvates thereof |
AU2008211711A1 (en) * | 2007-01-31 | 2008-08-07 | Generics [Uk] Limited | Process for the preparation of O-desmethyl venlafaxine |
IN2009DN05509A (en) * | 2007-03-14 | 2010-04-30 | Teva Pharma | |
CA2692738A1 (en) * | 2007-07-12 | 2009-01-15 | Dr. Reddy's Laboratories, Ltd. | O-desmethylvenlafaxine |
WO2009010990A2 (en) * | 2007-07-16 | 2009-01-22 | Matrix Laboratories Limited | Process for the preparation of o-desmethylvenlafaxine succinate polymorphic forms |
WO2009034434A2 (en) * | 2007-09-10 | 2009-03-19 | Cadila Pharmaceuticals Limited | An improved process for the preparation of o-desmethylvenlafaxine |
JP2011500777A (en) * | 2007-10-26 | 2011-01-06 | ジェネリクス・(ユーケー)・リミテッド | Method for producing O-desmethylvenlafaxine |
KR101343027B1 (en) * | 2007-11-26 | 2013-12-18 | 테바 파마슈티컬 인더스트리즈 리미티드 | Crystal forms of o-desmethylvenlafaxine fumarate |
WO2009084038A2 (en) * | 2007-12-28 | 2009-07-09 | Ind-Swift Laboratories Limited | Improved process for the preparation of 0-desmethyl-venlafaxine |
CA2717580A1 (en) * | 2008-03-06 | 2009-12-17 | Teva Pharmaceutical Industries Ltd. | Processes for the preparation of o-desmethylvenlafaxine, free from its dimer impurities |
EP2119695A1 (en) | 2008-05-16 | 2009-11-18 | Krka | Preparation of O-desmethylvenlafaxine salts |
EP2119696A1 (en) | 2008-05-16 | 2009-11-18 | Krka | Preparation of O-desmethylvenlafaxine salts |
KR20100132069A (en) * | 2008-06-16 | 2010-12-16 | 테바 파마슈티컬 인더스트리즈 리미티드 | Solid states of o-desmethylvenlafaxine salts |
US20100016638A1 (en) * | 2008-07-21 | 2010-01-21 | Zdenko Hamersak | Method for preparation of o-desmethylvenlafaxine using polythiolates |
CN102164886A (en) * | 2008-07-30 | 2011-08-24 | 基因里克斯(英国)有限公司 | Process for the preparation of O-desmethylvenlafaxine |
CZ2008756A3 (en) | 2008-11-27 | 2010-03-24 | Zentiva, A. S. | Process for preparing desvenlafaxine and salts thereof |
CZ301820B6 (en) | 2009-02-06 | 2010-06-30 | Zentiva, K.S. | Novel salts of desvenlafaxine and process of their preparation |
CZ2009454A3 (en) | 2009-07-15 | 2010-11-10 | Zentiva, K. S. | Process for preparing desvenlafaxine and salts thereof |
AU2010272377A1 (en) | 2009-07-16 | 2012-01-19 | Cipla Limited | Process for the preparation of O-desmethyl venlafaxine and intermediate for use therein |
US20110098506A1 (en) * | 2009-10-26 | 2011-04-28 | Intas Pharmaceuticals Limited | Method of preparing o-desmethylvenlafaxine |
US20110184067A1 (en) * | 2010-01-25 | 2011-07-28 | Intas Pharmaceuticals Ltd. | O-desmethylvenlafaxine succinate polymorph & process for preparing thereof |
KR101409554B1 (en) | 2010-03-29 | 2014-06-19 | 플리바 흐르바츠카 디.오.오. | Crystal forms of o-desmethylvenlafaxine fumarate |
CZ303249B6 (en) | 2010-04-06 | 2012-06-20 | Zentiva, K.S. | Process for preparing 4-(2-(substituted)-1-(1-hydroxycyclohexyl)ethyl)phenols by O-demethylation of their methyl ethers using odor free aromatic thiols |
EP2394976A1 (en) | 2010-06-11 | 2011-12-14 | LEK Pharmaceuticals d.d. | Process for demethylating aromatic methyl ethers using 3-mercaptopropionic acid |
WO2018146529A1 (en) | 2017-02-09 | 2018-08-16 | R L Finechem Private Limited | A process for preparation of1-[2-(dimethylamino)-1-(4-hydroxyphenyl) ethyl]-cyclohexanol and salts thereof |
CN109232189B (en) * | 2018-09-25 | 2021-10-08 | 杭州盛弗泰新材料科技有限公司 | Preparation method of high-purity 1-hydroxypyrene |
CN109665966A (en) * | 2018-11-01 | 2019-04-23 | 山东蒲济医药科技有限公司 | A kind of preparation method of succinic acid desmethylvenlafaxine compound |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4535186A (en) * | 1983-04-19 | 1985-08-13 | American Home Products Corporation | 2-Phenyl-2-(1-hydroxycycloalkyl or 1-hydroxycycloalk-2-enyl)ethylamine derivatives |
US4729817A (en) * | 1984-08-01 | 1988-03-08 | Tenneco Canada Inc. (Erco Division) | Process for the oxidative delignification of demethylated chemical pulp |
US5043466A (en) * | 1989-02-01 | 1991-08-27 | John Wyeth & Bro., Limited | Preparation of cyclohexanol derivatives and novel thioamide intermediates |
US6441048B1 (en) * | 1998-12-01 | 2002-08-27 | Sepracor, Inc. | Methods of treating affective disorders using derivatives of (-)-venlafaxine |
US6689912B2 (en) * | 2001-12-04 | 2004-02-10 | Wyeth | Methods for preparing O-desmethylvenlafaxine |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2741009A1 (en) * | 1976-09-22 | 1978-03-23 | Sandoz Ag | 4-STYRYL-4-INDOLINOL DERIVATIVES, THEIR USE AND PRODUCTION |
US6197828B1 (en) * | 1998-12-01 | 2001-03-06 | Sepracor, Inc. | Derivatives of (+)-venlafaxine and methods of preparing and using the same |
DE60039132D1 (en) | 1999-04-06 | 2008-07-17 | Sepracor Inc | O-desmethylvenlafaxine succinate |
WO2000076955A1 (en) | 1999-06-15 | 2000-12-21 | American Home Products Corporation | Enantiomers of o-desmethyl venlafaxine |
US20030171324A1 (en) | 2000-07-18 | 2003-09-11 | Shyam Ramakrishnan | Regulation of human desc1-like serine protease |
PT1360169E (en) * | 2001-02-12 | 2007-10-29 | Wyeth Corp | Succinate salt of o-desmethyl-venlafaxine |
-
2002
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- 2003-12-31 US US10/750,196 patent/US20040158101A1/en not_active Abandoned
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- 2004-05-31 IL IL162253A patent/IL162253A/en not_active IP Right Cessation
- 2004-06-01 CO CO04050957A patent/CO5580816A2/en active IP Right Grant
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- 2008-09-11 US US12/208,990 patent/US20090018365A1/en not_active Abandoned
- 2008-09-11 IL IL194034A patent/IL194034A/en not_active IP Right Cessation
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4535186A (en) * | 1983-04-19 | 1985-08-13 | American Home Products Corporation | 2-Phenyl-2-(1-hydroxycycloalkyl or 1-hydroxycycloalk-2-enyl)ethylamine derivatives |
US4729817A (en) * | 1984-08-01 | 1988-03-08 | Tenneco Canada Inc. (Erco Division) | Process for the oxidative delignification of demethylated chemical pulp |
US5043466A (en) * | 1989-02-01 | 1991-08-27 | John Wyeth & Bro., Limited | Preparation of cyclohexanol derivatives and novel thioamide intermediates |
US6441048B1 (en) * | 1998-12-01 | 2002-08-27 | Sepracor, Inc. | Methods of treating affective disorders using derivatives of (-)-venlafaxine |
US6689912B2 (en) * | 2001-12-04 | 2004-02-10 | Wyeth | Methods for preparing O-desmethylvenlafaxine |
US20040158101A1 (en) * | 2001-12-04 | 2004-08-12 | Wyeth | Methods for preparing O-desmethylvenlafaxine |
US7435854B2 (en) * | 2001-12-04 | 2008-10-14 | Wyeth | Methods for preparing O-desmethylvenlafaxine |
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