EP2121618A1 - Procédé de fabrication de composés hétérocycliques à substitution fluorométhyle - Google Patents

Procédé de fabrication de composés hétérocycliques à substitution fluorométhyle

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Publication number
EP2121618A1
EP2121618A1 EP07858009A EP07858009A EP2121618A1 EP 2121618 A1 EP2121618 A1 EP 2121618A1 EP 07858009 A EP07858009 A EP 07858009A EP 07858009 A EP07858009 A EP 07858009A EP 2121618 A1 EP2121618 A1 EP 2121618A1
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European Patent Office
Prior art keywords
alkyl
general formula
hydrogen
compounds
alkoxy
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EP07858009A
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German (de)
English (en)
Inventor
Thomas Zierke
Michael Rack
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BASF SE
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BASF SE
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Priority to EP07858009A priority Critical patent/EP2121618A1/fr
Publication of EP2121618A1 publication Critical patent/EP2121618A1/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

Definitions

  • the present invention relates to a process for the preparation of fluoromethyl-substituted heterocyclic compounds by reacting the corresponding chloromethyl-substituted compounds in the presence of fluorinating agents.
  • WO 2005/044804 describes lower alkyl esters of fluoromethyl-substituted heterocyclic carboxylic acids and their preparation by fluorination of the corresponding chloromethyl-substituted heterocyclic carboxylic acid esters and their further processing into the anilides of the fluoromethyl-substituted heterocyclic carboxylic acids.
  • the method is unsatisfactory in several respects.
  • the object of the present invention is thus to provide further fluoromethyl-substituted heterocyclic compounds, especially 3-difluoromethylpyrazol-4-yl or 3-trifluoromethylpyrazol-4-ylcarboxylic acid esters, and also processes for the preparation of these compounds.
  • These fluoromethyl-substituted pyrazol-4-ylcarboxylic acid esters should be distinguished by an improved convertibility into the corresponding amides.
  • the provision of the starting compounds for the preparation of the fluoromethyl-substituted pyrazol-4-ylcarbonklar with improved selectivity to the N-substitution is to be made possible.
  • heterocyclic carboxylic acid esters of the formulas I and II described below solve these objects and are thus advantageously suitable for the preparation of anilides of fluoromethyl-substituted heterocyclic carboxylic acids.
  • the present invention therefore provides fluoromethyl-substituted heterocyclic compounds of the general formula (I)
  • R 1 is hydrogen or fluorine
  • R 2 is a group - [AO] m -R 3 , in which
  • A is C 2 -C 4 -alkanediyl
  • R 3 is C 1 -C 4 -alkyl
  • n 1 or 2;
  • R 6 Al 4 is selected from C -C alkyl, d-Ce-haloalkyl, C 3 -C 6 cycloalkyl, Ci-C 4 alkoxy dC 4 alkyl, Ci-C4-alkylthio-Ci-C4- -alkyl, C 1 -C 4 -haloalkoxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, phenyl and benzyl, where the last two radicals optionally contain any combination of 1, 2 or 3 radicals R ⁇ 4 are independently selected from halogen, cyano, nitro, -C 4 - alkyl, Ci-C4-haloalkyl, Ci-C4-haloalkoxy may be substituted Ci-4 alkoxy and C;
  • R 1 ' is hydrogen or chlorine and R 2 and R 4 have the abovementioned meaning, in the presence of a fluorinating agent.
  • the compounds of the formula (I) according to the invention can be prepared in high yields, selectivities and purities. Another advantage is the high selectivity with respect to the position of the radical R 4 , since even the precursor of the formula (II) can be prepared with high regioselectivity. In addition, the inventive method allows the use of inexpensive starting materials. A further advantage is that both the work-up of the reaction mixtures obtained in the fluorination and the further reaction of the compounds of the formula (I) to give carboxylic acid amides can be carried out without difficulty.
  • the terms used for defining the variables for organic groups, such as the term "halogen", are generic terms that are representative of the individual members of these groups of organic entities.
  • the prefix C x -Cy denotes the number of possible carbon atoms in each case.
  • halogen refers to each of fluorine, bromine, chlorine or iodine, especially fluorine, chlorine or bromine.
  • C 1 -C 6 -alkyl as used herein and in the terms C 1 -C 6 -alkoxy, C 1 -C 6 -alkylamino, di (C 1 -C 6 -alkyl) amino, C 1 -C 6 -alkylthio C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -alkyl, oxyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, and C 1 -C 6 -alkylcarbonyloxy, denotes a saturated, straight-chain or branched hydrocarbon group comprising 1 to 6 carbon atoms, especially 1 to 4 carbon atoms, for example methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl, pentyl, 1-methylbutyl, 2-
  • C 1 -C 6 -haloalkyl as used herein and in the haloalkyl moieties of C 1 -C 6 -haloalkoxy, C 1 -C 6 -haloalkoxy-C 1 -C 6 -alkyl and haloalkylthio describes straight-chain or branched alkyl groups having 1 to 6 carbon atoms, wherein the hydrogen atoms of these groups are partially or completely replaced by halogen atoms, for example C 1 -C 4 haloalkyl, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1 Bromothyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-tri
  • C 1 -C 6 alkoxy describes straight-chain or branched saturated alkyl groups comprising 1 to 6 carbon atoms which are bonded via an oxygen atom.
  • Examples include C 1 -C 6 -alkoxy, such as, for example, methoxy, ethoxy, OCH 2 -C 2 H 5 , OCH (CH 2 ) 2 , n-butoxy, OCH (CH 3) -C 2 H 5 , OCH 2 -CH (CH 2 ) 2 , OC (CH 3 ) 3 , n -pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1, 1-dimethylpropoxy, 1, 2-dimethylpropoxy, 2,2-dimethylpropoxy , 1-ethylpropoxy, n-hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1, 1-dimethylbutoxy, 1, 2-dimethylbutoxy, 1, 3-dimethylbutoxy, 2,
  • C 1 -C 6 -haloalkoxy describes C 1 -C 6 -alkoxy groups as described above, wherein the hydrogen atoms of these groups are partially or completely replaced by halogen atoms, ie, for example, C 1 -C 6 -haloalkoxy such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-iodoethoxy, 2,2-difluoroethoxy, 2,2, 2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro
  • Ci-C4-alkoxy-Ci-C4-alkyl describes a Ci-C4-alkyl radical in which one hydrogen atom is replaced by a C 1 -C 4 -AIkOXy- radical.
  • Examples of these are CH 2 -OCH 3 , CH 2 -OC 2 H 5 , n-propoxymethyl, CH 2 -OCH (CH 2 ) 2 , n-butoxymethyl, (1-methylpropoxy) methyl, (2-methylpropoxy) methyl, CH 2 -OC (CH 3) S, 2- (methoxy) ethyl, 2- (ethoxy) ethyl, 2- (n-propoxy) ethyl, 2- (1-methylethoxy) ethyl, 2- (n-butoxy) ethyl, 2 - (1-methylpropoxy) ethyl, 2- (2-methylpropoxy) ethyl, 2- (1, 1-dimethylethoxy) ethyl, 2- (methoxy) propyl, 2- (ethoxy) propyl, 2- (n-propoxy ) propyl, 2- (1-methylethoxy) propyl, 2- (n-butoxy) propyl, 2- (1-methylpropoxy) propyl
  • C 1 -C 6 -alkylcarbonyl as used herein describes a straight-chain or branched saturated alkyl group comprising 1 to 6 carbon atoms which is terminally or internally bonded through the carbon atom of a carbonyl moiety.
  • Examples include C 1 -C 6 -alkylcarbonyls such as C (O) -CHs, C (O) -C 2 H 5 , n -propylcarbonyl, 1-methylethylcarbonyl, n-butylcarbonyl, 1-methylpropylcarbonyl, 2-methylpropylcarbonyl, 1, 1-dimethylethylcarbonyl, n-pentylcarbonyl, 1-methylbutylcarbonyl, 2-methylbutylcarbonyl, 3-methylbutylcarbonyl, 1, 1-dimethylpropylcarbonyl, 1, 2-dimethylpropylcarbonyl, 2,2-dimethylpropylcarbonyl, 1-ethylpropylcarbonyl, n-hexylcarbonyl, 1 Methylpentylcarbonyl, 2-methylpentylcarbonyl, 3-methylpentylcarbonyl, 4-methylpentylcarbonyl, 1, 1-dimethylbutylcarbonyl,
  • C 1 -C 6 alkoxycarbonyl as used herein describes a straight-chain or branched alkoxy group comprising 1 to 6 carbon atoms which is bonded via the carbon atom of a carbonyl unit.
  • Examples include (C 1 -C 6 -alkoxy) carbonyls, such as C (O) -OCH 3 , C (O) -OC 2 H 5 , C (O) -O-CH 2 -C 2 H 5 , C (O) -OCH (CHs) 2 , n-butoxycarbonyl, C (O) -OCH (CHs) -C 2 H 5 , C (O) -OCH 2 CH (CHs) 2 , C (O) -OC (CHs) 3 , n-pentoxycarbonyl, 1-methylbutoxycarbonyl, 2-methylbutoxycarbonyl, 3-methylbutoxycarbonyl, 2,2-dimethylpropoxycarbonyl, 1-ethylpropoxycarbonyl,
  • C 1 -C 6 -alkylcarbonyloxy as used herein describes straight-chain or branched saturated alkyl groups comprising 1 to 6 carbon atoms which is terminally or internally bonded through the carbon atom of the carbonyloxy moiety.
  • examples of examples include dC ⁇ -alkylcarbonyloxy, such as OC (O) -CH 3, O-C (O) H 5 , n-propylcarbonyloxy, 1-methylethylcarbonyloxy, n-butylcarbonyloxy, 1-methylpropylcarbonyl-oxy, 2-methylpropylcarbonyloxy, 1, 1-dimethylethylcarbonyloxy, n-pentylcarbonyloxy, 1-methylbutylcarbonyloxy, 2-methylbutylcarbonyloxy, 3-methylbutylcarbonyloxy, 1, 1-dimethylpropylcarbonyloxy, 1, 2-dimethylpropylcarbonyloxy, etc.
  • dC ⁇ -alkylcarbonyloxy such as OC (O) -CH 3, O-C (O) H 5 , n-propylcarbonyloxy, 1-methylethylcarbonyloxy, n-butylcarbonyloxy, 1-methylpropylcarbonyl-oxy
  • C 2 -C 6 alkenyl as used herein and for the alkenyl moieties of C 2 -C 6 alkenyloxy describes straight and branched unsaturated hydrocarbon radicals comprising 2 to 6 carbon atoms and at least one carbon-carbon double bond, such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2- Methyl 2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl 2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-buten
  • C 2 -C 6 alkenyloxy as used herein describes straight-chain or branched alkenyl groups comprising 2 to 6 carbon atoms which are bonded via an oxygen atom, such as vinyloxy, allyloxy (propen-3-yloxy), methallyl-oxy, Butene-4-yloxy, etc.
  • C 2 -C 6 alkynyl as used herein and in the alkynyl moieties of C 2 -C 6 alkynyloxy, C 2 -C 6 alkynylamino, C 2 -C 6 alkynylthio, C 2 -C 6 alkynylsulfonyl, C 2 -C 6 alkynylcarbonyl, C 2 -C 6 Alkynyloxycarbonyl and Ci-C ⁇ -alkynylcarbonyloxy, describes straight-chain and branched unsaturated hydrocarbons comprising 2 to 6 carbon atoms and at least one carbon-carbon triple bond, such as For example, ethynyl, prop-1-yn-1-yl, prop-2-yn-1-yl, n-but-1-yn-1-yl, n-but-1-yn-3-yl, n-But 1-yn-4-yl, n-but-2-yn-1-yl, n
  • Cs-Cs-cycloalkyl as used herein describes mono-, bi- or polycyclic hydrocarbon radicals comprising from 3 to 8 carbon atoms, especially 3 to 6 carbon atoms.
  • monocyclic radicals include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.
  • bicyclic radicals include bicyclo [2.2.1] heptyl, bicyclo [3.1.1] heptyl, bicyclo [2.2.2] octyl and bicyclo [3.2.1] octyl.
  • tricyclic radicals are adamantyl and homoadamantyl.
  • Each cycloalkyl radical may optionally be substituted with 1, 2, 3, 4 or 5 of the aforementioned radicals R # .
  • 1, 2, 3, 4 or 5 of the hydrogen atoms of these radicals may be independently replaced by the aforementioned radicals R # .
  • the substituents R # are of cycloalkyl radicals selected from halogen, especially fluorine or chlorine, or C 1 -C 6 -alkyl.
  • (C 2 -C 4) alkanediyl as used herein describes ethane-1, 2-diyl, propane-1, 3-diyl and butane-1, 4-diyl.
  • R 1 in the general formula (I) and R 1 'in the general formula (II) is hydrogen.
  • m is preferably 1.
  • radicals R 2 in which m is 1 are 2-methoxyethyl, 3-methoxypropyl, 4-methoxybutyl, 2-ethoxyethyl, 3-ethoxypropyl, 4-ethoxybutyl, 2- (propoxy) ethyl, 3- (propoxy ) propyl, 4- (propoxy) butyl, 2- (1-methylethoxy) ethyl, 3- (1-methylethoxy) propyl, 4- (1-methylethoxy) butyl, 2- (butoxy) ethyl, 3- (butoxy ) propyl, 4- (butoxy) -butyl, 2- (2-methylpropoxy) ethyl, 3- (2-methylpropoxy) propyl, 4- (2-methylpropoxy) butyl, 2- (1,2-dimethylethoxy) ethyl, 3 - (1, 2-dimethylethoxy) propyl and 4- (1, 2-dimethylethoxy) butyl, preferably 2-methoxye
  • halogen exchange reaction For the implementation of chloromethyl-substituted heterocyclic compound of the general formula (II) in the presence of a fluorinating agent (hereinafter referred to as halogen exchange reaction) are in principle all commonly used for halogen exchange reactions fluorinating agent.
  • the fluorination agent is preferably selected from alkali fluorides, such as sodium fluoride, potassium fluoride or cesium fluoride, cobalt (III) fluoride, antimony fluoride, molybdenum fluoride, hydrogen fluoride, hydrogen fluoride / pyridine mixtures, tertiary ammonium hydrofluorides or trialkylamine hydrofluorides of the general formula n * HF / N (Ci C 4 alkyl) 3, where n is 1, 2 or 3.
  • alkali fluorides such as sodium fluoride, potassium fluoride or cesium fluoride
  • cobalt (III) fluoride such as sodium fluoride, potassium fluoride or cesium fluoride
  • antimony fluoride such as sodium fluoride, potassium fluoride or cesium fluoride
  • molybdenum fluoride molybdenum fluoride
  • hydrogen fluoride hydrogen fluoride / pyridine mixtures
  • the fluorinating agent is particularly preferably selected from triethylamine tris-hydrofluoride, tri-n-butylamine tris-hydrofluoride and hydrogen fluoride / pyridine mixtures, in particular triethylamine tris-hydrofluoride and tri-n-butylamine tris-hydrofluoride.
  • the fluorinating agent is used in a molar ratio of fluoride equivalents per chlorine atom to be replaced in the range of 1: 1 to 3: 1.
  • the fluorinating agent is preferably used in a molar ratio in the range from 1: 1 to 1.5: 1.
  • the halogen exchange reaction preferably takes place at a temperature in the range from 80 to 170 ° C., in particular at a temperature in the range from 100 to 150 ° C.
  • the halogen exchange reaction can be carried out under atmospheric pressure or in the autoclave under autogenous pressure.
  • the pressure is preferably in the range from 0.1 to 50 bar, especially in the range from 1 to 10 bar.
  • Another object of the invention relates in addition to the halogen exchange reaction, the provision of the compound of general formula (II).
  • Pyrazole compounds of general formula (II) are accessible by reaction of 2-acyl-N, N-dialkyl-3-aminoacrylic acid ester (III) with hydrazine or suitable hydrazine derivatives.
  • hydrazine or hydrazine derivative is about equimolar, z. B. in a molar ratio (III): (hydrazine or hydrazine derivative) in the range of 0.8: 1 to 1: 1, 2 used.
  • the reaction is carried out in a dry inert solvent such as aromatic hydrocarbons z. As toluene, xylene, etc.
  • the reaction is usually carried out under a protective gas atmosphere z. B. under nitrogen.
  • hydrazine or the hydrazine derivative will be initially charged and, while cooling, a solution of the 3-aminoacrylic acid ester in an optionally dried inert solvent is added.
  • the isolation of the product is then carried out, if necessary, by suitable separation techniques, such as extraction, crystallization and / or column chromatography.
  • 2-acyl-N, N-dialkyl-3-aminoacrylic acid esters (III) can be provided by reacting 3-N, N-dialkylaminoacrylic acid esters with halogenated acetyl chlorides.
  • the reaction is carried out in an inert solvent, such as toluene.
  • the molar ratio of diethylaminoacrylic acid ester to the halogenated acetyl chloride is typically in the range of 0.8: 1 to 1: 1.2, and is more preferably about equimolar.
  • dialkylaminoacrylic acid ester will be initially charged in an inert solvent and the haloge- ned acetyl chloride as a solution slowly add with cooling.
  • the isolation of the product of the reaction is then carried out by conventional separation methods, as mentioned above.
  • 3-N, N-Dimethylaminoacryl Acidester turn can be prepared from the alkali metal salts of formylacetic acid esters, in particular from the sodium salts, by reaction with hydrochlorides of secondary amines, especially dimethylamine hydrochloride provide.
  • hydrochlorides of secondary amines especially dimethylamine hydrochloride provide.
  • the hydrochloride of the secondary amine is initially charged in an inert, non-polar solvent and a solution of the salt of formylacetic acid ester is added slowly.
  • the molar ratio of (alkali salt of Formylessigkla- ester): (hydrochloride of the secondary amine) is usually in the range of 0.8: 1, 2 to 1: 1, 2, in particular, the two compounds are used approximately equimolar.
  • the by-produced salt precipitates it may be removed after completion of the reaction by a suitable method such as filtration and the filtrate comprising the desired reaction product is devolatilized, for example by evaporation. If necessary, the reaction product is isolated from the residue by suitable separation methods.
  • Another object of the present invention therefore relates to processes for the preparation of compounds of general formula (II), wherein a compound of general formula (III), wherein R 1 'and R 2 have the meaning given above, in the presence of hydrazine or a Hydrazine derivative of the formula (Ci-C4-alkyl) N HN H2.
  • methylhydrazine is used for this purpose.
  • the compounds of the general formula (I) according to the invention are advantageously suitable for the synthesis of a large number of compounds of interest as active ingredients, for example fungicidal carboxamides.
  • Another aspect of the invention relates to a process for the preparation of amides of the general formula (IV),
  • R 1 and R 4 have the previously given meaning
  • R 5 is selected from C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 8 -cycloalkyl,
  • R 6 is selected from hydrogen, halogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy,
  • n 1, 2, 3 or 4;
  • R 7 is selected from C 1 -C 20 -alkyl, C 2 -C 20 -alkenyl, C 2 -C 20 -alkynyl, which may be optionally substituted by a combination of radicals R ay ,
  • R ay are independently selected from halogen, cyano, nitro, hydroxy, mercapto, amino, carboxyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkenyloxy, C 2 -C 6 -alkynyloxy, C 1 -C 6 -haloalkoxy , C 1 -C 6 -alkylthio, C 1 -C 6 -alkylamino, di (C 1 -C 6 -alkyl) amino, C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -alkylsulfoxyl, formyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylthio Alkoxycarbonyl, formyloxy and Ci-Ce-alkylcarbonyloxy;
  • R ax are independently selected from halo, cyano, nitro, hydroxy, mercapto, amino, carboxyl, d-Ce-alkyl, d-Ce-haloalkyl, C 3 -C 6 cycloalkyl, Ci-C 6 alkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 alkynyloxy, Ci-C 6 haloalkoxy, Ci-C 6 alkylthio, Ci-Ce-alkylamino, di (Ci-C 6 alkyl) amino, d-Ce Alkylsulfonyl, C 1 -C 6 -alkyl, oxyl, formyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, formyloxy and C 1 -C 6 -alkylcarbonyloxy; and wherein at least one fluoromethyl-substituted heterocyclic compound of
  • esters to amides are known to those skilled in the art.
  • the ester function of the compounds of the general formula (I) can be converted in the presence of an acid or base, preferably in the presence of a base, by saponification into the free carboxylic acid or into the corresponding carboxylate anion.
  • the carboxylic acid can then be converted under suitable reaction conditions with a corresponding aniline derivative directly into a compound of general formula (IV) or, if appropriate, can be converted before the reaction with the aniline derivative in a more reactive species, for example in an acid chloride.
  • the coupling reaction of carboxylic acid and aniline derivative can optionally be carried out in the presence of catalysts, condensing agents, acid binding agents and / or with water separation, for example by azeotropic distillation.
  • catalysts for this and for the isolation of the desired product of general formula (IV) are known in the art.
  • Methylhydrazine (3.8 g, 0.08 mol) was placed in dry toluene (90 ml) under nitrogen and cooled to about 0 0 C. At this temperature, a solution of 4,4-dichloro-2- (N, N-dimethylaminomethylene) acetoacetic acid (2-methoxyethyl) ester (23 g, 0.08 mol) in dry toluene (90 mL) over a period of / 4 hours slowly dripped. After completion of the addition, stirring was WEI tere 3 hours at 0 0 C and then warmed to room temperature.
  • reaction solution was washed with water (100 ml).
  • the washing phase was extracted with toluene (100 ml), the two organic phases were combined and freed of the volatiles under reduced pressure.
  • the residue was purified by column chromatography (SiO 2, ethyl acetate: petroleum ether, 1: 1) and analyzed by GC control and 1 H-NMR.
  • the desired product was obtained with a yield of 7.7 g (0.03 mol) in a purity of 95.5 Fl. % receive.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

La présente invention concerne un procédé de fabrication de composés hétérocycliques à substitution fluorométhyle de formule générale (I), dans laquelle R<SUP>1</SUP> représente H ou F ; R<SUP>2</SUP> représente un groupement -[A-O]<SUB>m</SUB>-R<SUP>3</SUP>, dans lequel A représente un alcanediyle en C<SUB>2</SUB>-C<SUB>4</SUB>, R<SUP>3</SUP> représente un alkyle en C<SUB>1</SUB>-C<SUB>4</SUB> et m vaut 1 ou 2 ; par réaction des composés à substitution chlorométhyle (II) correspondants en présence d'agents de fluoration. L'invention concerne également un procédé de fabrication des composés à substitution chlorométhyle (II), un procédé de fabrication d'amides des formules générales (IV), ainsi que des composés des formules générales (I) et (II).
EP07858009A 2006-12-21 2007-12-20 Procédé de fabrication de composés hétérocycliques à substitution fluorométhyle Withdrawn EP2121618A1 (fr)

Priority Applications (1)

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EP07858009A EP2121618A1 (fr) 2006-12-21 2007-12-20 Procédé de fabrication de composés hétérocycliques à substitution fluorométhyle

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP06126937 2006-12-21
PCT/EP2007/064390 WO2008077907A1 (fr) 2006-12-21 2007-12-20 Procédé de fabrication de composés hétérocycliques à substitution fluorométhyle
EP07858009A EP2121618A1 (fr) 2006-12-21 2007-12-20 Procédé de fabrication de composés hétérocycliques à substitution fluorométhyle

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US (1) US7994207B2 (fr)
EP (1) EP2121618A1 (fr)
JP (1) JP2010513411A (fr)
KR (1) KR20090107506A (fr)
CN (1) CN101558044A (fr)
AR (1) AR064631A1 (fr)
AU (1) AU2007338031B2 (fr)
BR (1) BRPI0720410A2 (fr)
CA (1) CA2671527A1 (fr)
EA (1) EA200900817A1 (fr)
IL (1) IL199124A (fr)
MX (1) MX2009005863A (fr)
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AU2009245791B2 (en) 2008-05-08 2013-05-16 Basf Se Method for manufacturing aryl carboxamides
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EA200900817A1 (ru) 2009-12-30
BRPI0720410A2 (pt) 2013-12-31
CN101558044A (zh) 2009-10-14
KR20090107506A (ko) 2009-10-13
MX2009005863A (es) 2009-06-12
IL199124A (en) 2013-05-30
US20100022782A1 (en) 2010-01-28
WO2008077907A1 (fr) 2008-07-03
UA96971C2 (ru) 2011-12-26
AU2007338031B2 (en) 2012-08-16
US7994207B2 (en) 2011-08-09
CA2671527A1 (fr) 2008-07-03
JP2010513411A (ja) 2010-04-30
AU2007338031A1 (en) 2008-07-03

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