WO2006031764A2 - Processes for prepating n-(substituted arylmethyl)-4-(disubstituted methyl)piperidines and intermediates - Google Patents
Processes for prepating n-(substituted arylmethyl)-4-(disubstituted methyl)piperidines and intermediates Download PDFInfo
- Publication number
- WO2006031764A2 WO2006031764A2 PCT/US2005/032473 US2005032473W WO2006031764A2 WO 2006031764 A2 WO2006031764 A2 WO 2006031764A2 US 2005032473 W US2005032473 W US 2005032473W WO 2006031764 A2 WO2006031764 A2 WO 2006031764A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- compound
- ocf
- group
- halogen
- Prior art date
Links
- 0 *c1ccc(C(C2CCNCC2)O)cc1 Chemical compound *c1ccc(C(C2CCNCC2)O)cc1 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- This invention is in the field of chemical processes; more specifically, processes for preparing intermediates useful in the preparation of N-(substituted arylmethyl)-4-(disubstituted methyl)piperidines.
- N-(substituted arylmethyl)-4-(disubstituted methyl)piperidines are disclosed in PCT publications 2004/060371 and 2004/060865 as useful insecticides the disclosures of which are incorporated herein by reference.
- PCT publication 2004/060371 discloses the following general process for synthesizing N-(substituted arylmethyl)-4-(disubstituted methyl)piperidines :
- Disadvantages of this process include less than optimal yields, less than optimal cycle times and high catalyst loadings.
- Another disadvantage is the highly exothermic first step of the reaction. This significant exothermic reaction is a result of the presence of Mg and fluorine. Marginally controllable, highly exothermic reactions can affect yields and cycle times as well as require costly equipment.
- the present invention improves yield, cycle times and catalyst loading as well as reduces the exothermic nature of certain of the reactions involved in producing N- (substituted arylmethyl)-4-(disubstituted methyl)piperidines.
- the present invention relates to improved processes for preparing intermediates useful in preparing N-(substituted arylmethyl)-4-(disubstituted methyi)piperidines.
- R 1 is selected from the group consisting of halogen, CF 3 , OCF 3 , OCHF 2 , OCF 2 CHF 2 and SF 5 ;
- R 1 is as defined above;
- the reaction can be conducted in a solvent, preferably tetrahydrofuran, dioxane or monoglyme.
- the alkyl magnesium halide is z-propyl magnesium chloride or /-propyl magnesium bromide.
- R 1 is selected from the group consisting of halogen, CF 3 , OCF 3 , OCHF 2 , OCF 2 CHF 2 and SF 5 ;
- the hydrating can be conducted with a metal catalyst; in an alcohol solvent.
- the metal catalyst is platinum, palladium or rhodium; the alcohol solvent is methanol or ethanol.
- the elevated pressure is in the range of from 25 pounds per square inch to 200 pounds per square inch.
- a third embodiment of the present invention is an improved process for preparing a compound of formula F:
- R 1 is selected from the group consisting of halogen, CF 3 , OCF 3 , OCHF 2 , OCF 2 CHF 2 and SF 5 ;
- Z and B are independently selected from the group consisting of CH and N;
- Y is halogen
- the reaction can be conducted at a temperature in the range of from ambient temperature to 80°C.
- the solvent is preferably toluene or methyl isobutyl ketone.
- the phase transfer catalyst can be polyethylene glycol, dimethylaminopyridine, triethylamine,/?-toluenesulfonic acid, phosphorous pentoxide, pyridine or phase transfer catalysts such as quaternary ammonium salts or quaternary phosphonium salts or mixtures thereof.
- reaction of a compound of formula C and a compound of formula D is conducted in the presence of a sodium borohydride and a solvent selected from the group consisting of 1,2-dichloroethane, dichloromethane, acetonitrile and tetrahydrofuran.
- a sodium borohydride selected from the group consisting of 1,2-dichloroethane, dichloromethane, acetonitrile and tetrahydrofuran.
- R 1 and R 2 are independently selected from the group consisting of halogen, CF 3 , OCF 3 , OCHF 2 , OCF 2 CHF 2 and SF 5 ; and Z and B are independently selected from the group consisting of CH and N;
- R 1 , Z and B are as defined above;
- R is as defined above;
- a solvent selected from the group consisting of 1,2- dichloroethane, acetonitrile and dioxane.
- the condensing can be conducted at a temperature in the range of from 40°C to 80°C.
- R 1 and R 2 are independently selected from the group consisting of halogen, CF 3 , and OCF 3 ;
- X is bromine or chlorine;
- Y is bromine, iodine or chlorine. More preferably, R 1 is CF 3 and R 2 is Cl;
- X is bromine.
- Z is N and B is CH.
- the "about” range shall be not more than 10% of the absolute value of an end point or 10% of the range recited, whichever is less.
- alkyl As used in this specification and unless otherwise indicated the substituent terms "alkyl”, “alkoxy”, and “haloalkyl”, used alone or as part of a larger moiety, includes straight or branched chains of at least one or two carbon atoms, as appropriate to the substituent, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms.
- aryl refers to phenyl or naphthyl optionally substituted with one or more halogen, alkyl, alkoxy, or haloalkyl.
- Halogen “halide” or “halo” refers to fluorine, bromine, iodine, or chlorine.
- ambient temperature refers to a temperature in the range of from about 20° C to about 30° C.
- Certain solvents, catalysts, and the like are known by their acronyms. These include the acronyms “EDC” meaning 1,2- dichloroethane and “THF” meaning tetrahydrofuran.
- Glymes refers to a class of solvents comprised of monoglyme, diglyme, triglyme, tetraglyme, and polyglyme.
- R 1 is CF
- an appropriately substituted phenol for example, the known compound 4-methyl phenol
- a halopyridine for example 2-chloropyridine
- potassium carbonate for example potassium carbonate
- a catalytic amount of copper oxide at a temperature in the range of from 145°C to 170°C
- D2 2-(4-methylphenoxy)pyridine
- D2 can then be halogenated with, for example bromine, to form 2-[4- (bromomethyl)phenoxy]pyridine (E).
- Intermediate (F) can then be condensed with an appropriately substituted aryl halide, for example the known compound 4-chlorobenxenisocyanate (G), at a temperature in the range of from 35°C to 50 0 C to form N-(4-chlorophenyl)( ⁇ l-[(4- (2-pyridyloxy)phenyl)methyl](4-piperidyl) ⁇ [4-
- an appropriately substituted aryl halide for example the known compound 4-chlorobenxenisocyanate (G)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2007531438A JP2008512495A (en) | 2004-09-13 | 2005-09-12 | Process for preparing N- (substituted arylmethyl) -4- (disubstituted methyl) piperidines and intermediates |
EP05798202A EP1794144A2 (en) | 2004-09-13 | 2005-09-12 | Processes for prepating n-(substituted arylmethyl)-4-(disubstituted methyl)piperidines and intermediates |
BRPI0515275-5A BRPI0515275A (en) | 2004-09-13 | 2005-09-12 | processes for the preparation of n- (substituted arylmethyl) -4- (methyl disubstituted) piperidines and intermediates |
IL181102A IL181102A0 (en) | 2004-09-13 | 2007-02-01 | Processes for preparing n-(substituted arylmethyl)-4-(disubstituted methyl)piperidines and intermediates |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US60953904P | 2004-09-13 | 2004-09-13 | |
US60/609,539 | 2004-09-13 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2006031764A2 true WO2006031764A2 (en) | 2006-03-23 |
WO2006031764A3 WO2006031764A3 (en) | 2006-07-13 |
Family
ID=36060625
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2005/032473 WO2006031764A2 (en) | 2004-09-13 | 2005-09-12 | Processes for prepating n-(substituted arylmethyl)-4-(disubstituted methyl)piperidines and intermediates |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP1794144A2 (en) |
JP (1) | JP2008512495A (en) |
KR (1) | KR20070052319A (en) |
CN (1) | CN101018776A (en) |
AR (1) | AR052977A1 (en) |
BR (1) | BRPI0515275A (en) |
IL (1) | IL181102A0 (en) |
TW (1) | TW200621747A (en) |
WO (1) | WO2006031764A2 (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1314955A (en) * | 1970-11-27 | 1973-04-26 | Richardson Merrell Inc | 4-4-alpha-hydroxybenzyl piperidino 4-fluorobutyrophenone derivative |
WO2004060371A1 (en) * | 2002-12-18 | 2004-07-22 | Fmc Corporation | N-(substituted arylmethyl)-4-(disubstituted methyl) piperidines and pyridines |
-
2005
- 2005-09-12 EP EP05798202A patent/EP1794144A2/en active Pending
- 2005-09-12 KR KR1020077006338A patent/KR20070052319A/en not_active Application Discontinuation
- 2005-09-12 JP JP2007531438A patent/JP2008512495A/en not_active Withdrawn
- 2005-09-12 WO PCT/US2005/032473 patent/WO2006031764A2/en active Application Filing
- 2005-09-12 TW TW094131305A patent/TW200621747A/en unknown
- 2005-09-12 CN CNA2005800307540A patent/CN101018776A/en active Pending
- 2005-09-12 BR BRPI0515275-5A patent/BRPI0515275A/en not_active Application Discontinuation
- 2005-09-12 AR ARP050103799A patent/AR052977A1/en unknown
-
2007
- 2007-02-01 IL IL181102A patent/IL181102A0/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1314955A (en) * | 1970-11-27 | 1973-04-26 | Richardson Merrell Inc | 4-4-alpha-hydroxybenzyl piperidino 4-fluorobutyrophenone derivative |
WO2004060371A1 (en) * | 2002-12-18 | 2004-07-22 | Fmc Corporation | N-(substituted arylmethyl)-4-(disubstituted methyl) piperidines and pyridines |
Non-Patent Citations (1)
Title |
---|
SHANKLIN J.R. ET AL.: 'Synthesis, Calcium-Channel-Blocking Activity, and Antihypertensive Activity of 4-(Diarylmethyl)-1-[3-(aryloxy)propylÜpiper idines and Structurally Related Compounds' J. MED. CHEM. vol. 34, May 1991, pages 3011 - 3022, XP002241320 * |
Also Published As
Publication number | Publication date |
---|---|
KR20070052319A (en) | 2007-05-21 |
EP1794144A2 (en) | 2007-06-13 |
WO2006031764A3 (en) | 2006-07-13 |
TW200621747A (en) | 2006-07-01 |
AR052977A1 (en) | 2007-04-18 |
BRPI0515275A (en) | 2008-07-15 |
JP2008512495A (en) | 2008-04-24 |
CN101018776A (en) | 2007-08-15 |
IL181102A0 (en) | 2007-07-04 |
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