WO2008055849A1 - Process for the preparation of trifluoroethoxytoluenes - Google Patents
Process for the preparation of trifluoroethoxytoluenes Download PDFInfo
- Publication number
- WO2008055849A1 WO2008055849A1 PCT/EP2007/061818 EP2007061818W WO2008055849A1 WO 2008055849 A1 WO2008055849 A1 WO 2008055849A1 EP 2007061818 W EP2007061818 W EP 2007061818W WO 2008055849 A1 WO2008055849 A1 WO 2008055849A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- trifluoroethoxy
- toluene
- formula
- preparation
- trifluoroethanol
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/09—Preparation of ethers by dehydration of compounds containing hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/205—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring
- C07C43/2055—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring containing more than one ether bond
Definitions
- the present invention relates to an novel process for the preparation a substituted 1 ,4-£/s(2,2,2-trifluoroethoxy)benzene of the formula (I)
- 2,5-6/s(2,2,2-trifluoroethoxy)toluene is a derivative of 1 ,4-6/5(2,2,2- trifluoroethoxy)benzene, which as well is used as intermediate for synthesis of Flecainide.
- £/s(2,2,2-trifluoroethoxy)benzene is that the process requires the reaction of 8 equivalents of 2,2,2-trifluoroethanol while only 2 equivalents are theoretically needed.
- the use of less than 8 equivalents of 2,2,2- trifluoroethanol results in incomplete conversion to 1 ,4-£/s(2,2,2- trifluoroethoxy)benzene, with the starting material and 1-bromo-4-(2,2,2- trifluoroethoxy)benzene as the main impurities. Isolation and purification of desired product from this mixture is not practical on an industrial scale.
- Another method involves the process to obtained the 1 ,4-£/s(2,2,2- trifluoroethoxy)benzene (III) is by the reaction of 4-fluoro-1-bromobenzene with 2,2,2-trifluoroethanol in the presence of sodium hydride, N 1 N- dimethylformamide and CuBr 2 at about 100-105 0 C WO 02/066413 (NARCHEM CORPORATION) 2002.02.20. .
- the method of the present invention involves the novel initial preparation of 2,5-£/s(2,2,2-trifluoroethoxy)toluene by reaction 2,5-dihalotoluene with 2,2,2-trifluoroethanol in the presence alkali metal and copper containing material.
- the 2,2,2-trifluoroathanol reacts in about 2-10 fold molar excess of the 2,5-dihalotoluene to replace the 2,5-dihalotoluene aromatic halogen substituents with trifluoroethoxy groups.
- Bases that enable the reaction include alkali metals, e.g., metallic sodium.
- a copper containing material is used as a catalyst in the reaction, e.g., copper (II) sulphate.
- ⁇ /, ⁇ /-dimethylformamide can be used as an dipolar aprotic solvent.
- the best mode for carrying out the reaction is a temperature of about 85 to 105 0 C.
- the 2,5-£/s(2,2,2-trifluoroethoxy)toluene [II] can be used as intermediate in pharmaceutical industry.
- 2,5-b/s ⁇ 2, 2, 2-trifluoroethoxy)toluene as intermediate yield of Flecainide [III] and pharmaceutically acceptable salts can be increased to 86%.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Catalysts (AREA)
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009535081A JP2010508330A (en) | 2006-11-06 | 2007-11-02 | Preparation of trifluoroethoxytoluenes |
AT07847103T ATE514670T1 (en) | 2006-11-06 | 2007-11-02 | METHOD FOR PRODUCING TRIFLUORETHOXYTOLUENES |
US12/312,323 US20100063292A1 (en) | 2006-11-06 | 2007-11-02 | Process for the preparation of trifluoroethoxytoluenes. |
MX2009004647A MX2009004647A (en) | 2006-11-06 | 2007-11-02 | Process for the preparation of trifluoroethoxytoluenes. |
EP07847103A EP2079674B1 (en) | 2006-11-06 | 2007-11-02 | Process for the preparation of trifluoroethoxytoluenes |
EA200900357A EA200900357A1 (en) | 2006-11-06 | 2007-11-02 | METHOD OF OBTAINING TRIFTOROETOXYTOLUOLES |
PL07847103T PL2079674T3 (en) | 2006-11-06 | 2007-11-02 | Process for the preparation of trifluoroethoxytoluenes |
BRPI0714991-3A BRPI0714991A2 (en) | 2006-11-06 | 2007-11-02 | process for the preparation of trifluroethoxytoluenes |
CA002660358A CA2660358A1 (en) | 2006-11-06 | 2007-11-02 | Process for the preparation of trifluoroethoxytoluenes |
AU2007316690A AU2007316690A1 (en) | 2006-11-06 | 2007-11-02 | Process for the preparation of trifluoroethoxytoluenes |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06123547.9 | 2006-11-06 | ||
EP06123547A EP1918280A1 (en) | 2006-11-06 | 2006-11-06 | Process for the preparation of 2,5-bis-(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)-benzamide and salts thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2008055849A1 true WO2008055849A1 (en) | 2008-05-15 |
Family
ID=37965028
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2007/061818 WO2008055849A1 (en) | 2006-11-06 | 2007-11-02 | Process for the preparation of trifluoroethoxytoluenes |
PCT/EP2007/061820 WO2008055851A1 (en) | 2006-11-06 | 2007-11-02 | Process for the preparation of 2,5-bis-(2,2,2-trifluoroethoxy)-n-(2-piperidylmethyl)-benzamide and salts thereof |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2007/061820 WO2008055851A1 (en) | 2006-11-06 | 2007-11-02 | Process for the preparation of 2,5-bis-(2,2,2-trifluoroethoxy)-n-(2-piperidylmethyl)-benzamide and salts thereof |
Country Status (14)
Country | Link |
---|---|
US (2) | US20100056794A1 (en) |
EP (3) | EP1918280A1 (en) |
JP (2) | JP2010508331A (en) |
KR (2) | KR20090055638A (en) |
CN (2) | CN101516817A (en) |
AT (1) | ATE514670T1 (en) |
AU (2) | AU2007316692A1 (en) |
BR (2) | BRPI0714989A2 (en) |
CA (2) | CA2660364A1 (en) |
EA (2) | EA200900356A1 (en) |
MX (2) | MX2009004648A (en) |
PL (1) | PL2079674T3 (en) |
WO (2) | WO2008055849A1 (en) |
ZA (2) | ZA200902183B (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102977003A (en) * | 2012-11-28 | 2013-03-20 | 郑州大明药物科技有限公司 | Preparation method of flecainide acetate |
CN111018694A (en) * | 2019-12-12 | 2020-04-17 | 贵州省欣紫鸿药用辅料有限公司 | Production method of flecainide |
CN115368786B (en) * | 2022-08-15 | 2023-05-09 | 江阴市华昌不锈钢管有限公司 | Preparation process of super austenitic high-temperature-resistant corrosion-resistant stainless steel welded pipe |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3900481A (en) * | 1974-04-01 | 1975-08-19 | Riker Laboratories Inc | Derivatives of pyrrolidine and piperidine |
WO1998047853A1 (en) * | 1997-04-21 | 1998-10-29 | Finetech Ltd. | Process for the preparation of trifluoroethoxyarenecarboxylic acids |
WO2001090062A2 (en) * | 2000-05-26 | 2001-11-29 | Merck Patent Gmbh | Method for the production of trifluoroethoxy-substituted benzoic acids |
WO2002004419A2 (en) * | 2000-07-12 | 2002-01-17 | Geneva Pharmaceuticals, Inc. | α,α-DIBROMO-α-CHLORO-ACETOPHENONES AS SYNTHONS |
EP1283201A1 (en) * | 2001-08-10 | 2003-02-12 | A.M.S.A. ANONIMA MATERIE SINTETICHE E AFFINI S.p.A. | Process for the preparation of 2,5-bis-(2,2,2-trifluoroethoxy)-n-(2-piperidyl-methyl)-benzamide (flecanide) |
US20050059825A1 (en) * | 2003-09-17 | 2005-03-17 | Zhi-Xian Wang | Novel process for the preparation of flecainide, its pharmaceutically acceptable salts and important intermediates thereof |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4617396A (en) * | 1979-03-19 | 1986-10-14 | Riker Laboratories, Inc. | Process for the preparation of derivatives of piperidine |
-
2006
- 2006-11-06 EP EP06123547A patent/EP1918280A1/en not_active Withdrawn
-
2007
- 2007-11-02 EA EA200900356A patent/EA200900356A1/en unknown
- 2007-11-02 CA CA002660364A patent/CA2660364A1/en not_active Abandoned
- 2007-11-02 AU AU2007316692A patent/AU2007316692A1/en not_active Abandoned
- 2007-11-02 KR KR1020097007909A patent/KR20090055638A/en not_active Application Discontinuation
- 2007-11-02 CA CA002660358A patent/CA2660358A1/en not_active Abandoned
- 2007-11-02 CN CNA2007800358109A patent/CN101516817A/en active Pending
- 2007-11-02 CN CNA2007800358537A patent/CN101516845A/en active Pending
- 2007-11-02 BR BRPI0714989-1A patent/BRPI0714989A2/en not_active Application Discontinuation
- 2007-11-02 MX MX2009004648A patent/MX2009004648A/en not_active Application Discontinuation
- 2007-11-02 WO PCT/EP2007/061818 patent/WO2008055849A1/en active Application Filing
- 2007-11-02 EA EA200900357A patent/EA200900357A1/en unknown
- 2007-11-02 EP EP07847103A patent/EP2079674B1/en active Active
- 2007-11-02 PL PL07847103T patent/PL2079674T3/en unknown
- 2007-11-02 KR KR1020097007916A patent/KR20090064456A/en not_active Application Discontinuation
- 2007-11-02 AT AT07847103T patent/ATE514670T1/en not_active IP Right Cessation
- 2007-11-02 MX MX2009004647A patent/MX2009004647A/en not_active Application Discontinuation
- 2007-11-02 US US12/312,322 patent/US20100056794A1/en not_active Abandoned
- 2007-11-02 EP EP07822153A patent/EP2079692A1/en not_active Withdrawn
- 2007-11-02 AU AU2007316690A patent/AU2007316690A1/en not_active Abandoned
- 2007-11-02 US US12/312,323 patent/US20100063292A1/en not_active Abandoned
- 2007-11-02 WO PCT/EP2007/061820 patent/WO2008055851A1/en active Application Filing
- 2007-11-02 JP JP2009535082A patent/JP2010508331A/en active Pending
- 2007-11-02 JP JP2009535081A patent/JP2010508330A/en active Pending
- 2007-11-02 BR BRPI0714991-3A patent/BRPI0714991A2/en not_active Application Discontinuation
-
2009
- 2009-04-16 ZA ZA200902183A patent/ZA200902183B/en unknown
- 2009-04-16 ZA ZA200902184A patent/ZA200902184B/en unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3900481A (en) * | 1974-04-01 | 1975-08-19 | Riker Laboratories Inc | Derivatives of pyrrolidine and piperidine |
WO1998047853A1 (en) * | 1997-04-21 | 1998-10-29 | Finetech Ltd. | Process for the preparation of trifluoroethoxyarenecarboxylic acids |
WO2001090062A2 (en) * | 2000-05-26 | 2001-11-29 | Merck Patent Gmbh | Method for the production of trifluoroethoxy-substituted benzoic acids |
WO2002004419A2 (en) * | 2000-07-12 | 2002-01-17 | Geneva Pharmaceuticals, Inc. | α,α-DIBROMO-α-CHLORO-ACETOPHENONES AS SYNTHONS |
EP1283201A1 (en) * | 2001-08-10 | 2003-02-12 | A.M.S.A. ANONIMA MATERIE SINTETICHE E AFFINI S.p.A. | Process for the preparation of 2,5-bis-(2,2,2-trifluoroethoxy)-n-(2-piperidyl-methyl)-benzamide (flecanide) |
US20050059825A1 (en) * | 2003-09-17 | 2005-03-17 | Zhi-Xian Wang | Novel process for the preparation of flecainide, its pharmaceutically acceptable salts and important intermediates thereof |
Also Published As
Publication number | Publication date |
---|---|
KR20090055638A (en) | 2009-06-02 |
BRPI0714989A2 (en) | 2013-07-30 |
ATE514670T1 (en) | 2011-07-15 |
MX2009004647A (en) | 2009-05-20 |
ZA200902184B (en) | 2010-03-31 |
AU2007316692A1 (en) | 2008-05-15 |
ZA200902183B (en) | 2010-07-28 |
CA2660364A1 (en) | 2008-05-15 |
PL2079674T3 (en) | 2011-11-30 |
CN101516845A (en) | 2009-08-26 |
AU2007316690A1 (en) | 2008-05-15 |
EA200900357A1 (en) | 2009-10-30 |
KR20090064456A (en) | 2009-06-18 |
JP2010508330A (en) | 2010-03-18 |
EP2079674B1 (en) | 2011-06-29 |
MX2009004648A (en) | 2009-05-21 |
WO2008055851A8 (en) | 2009-04-09 |
BRPI0714991A2 (en) | 2013-07-30 |
WO2008055851A1 (en) | 2008-05-15 |
US20100063292A1 (en) | 2010-03-11 |
JP2010508331A (en) | 2010-03-18 |
EA200900356A1 (en) | 2009-10-30 |
EP1918280A1 (en) | 2008-05-07 |
CN101516817A (en) | 2009-08-26 |
EP2079692A1 (en) | 2009-07-22 |
EP2079674A1 (en) | 2009-07-22 |
CA2660358A1 (en) | 2008-05-15 |
US20100056794A1 (en) | 2010-03-04 |
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