WO2021228673A1 - Procédé de préparation d'isoxazolines optiquement enrichies - Google Patents

Procédé de préparation d'isoxazolines optiquement enrichies Download PDF

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WO2021228673A1
WO2021228673A1 PCT/EP2021/061970 EP2021061970W WO2021228673A1 WO 2021228673 A1 WO2021228673 A1 WO 2021228673A1 EP 2021061970 W EP2021061970 W EP 2021061970W WO 2021228673 A1 WO2021228673 A1 WO 2021228673A1
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alkyl
crc
ring
alkenyl
partially
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PCT/EP2021/061970
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English (en)
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Kailaskumar Borate
Karsten Koerber
Nikolas HUWYLER
Birgit GOCKEL
Ritesh KARALKAR
Harish SHINDE
Roland Goetz
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Basf Se
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • C07D453/04—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems having a quinolyl-4, a substituted quinolyl-4 or a alkylenedioxy-quinolyl-4 radical linked through only one carbon atom, attached in position 2, e.g. quinine

Definitions

  • the invention relates to a process for the preparation of optically enriched isoxazoline compounds of formula I wherein
  • R 1 is halomethyl
  • R 2a is F, Cl, Br, or OCF 3 .
  • R 2b and R 2c are H, or as defined for R 2a ;
  • R 4 H halogen, CN, N 3 , NO2, SCN, SF 5 , CrCe-alkyl, C 3 -C 8 -cycloalkyl, C2-Ce-alkenyl, C2- Ce-alkynyl, OR 9 , or S(0) n R 9 ;
  • W is O or S
  • R 5 is independently selected from the meanings mentioned for R 4 ;
  • R i ° a i o b are independently from one another H, CrC 6 -alkyl, CrC 6 -haloalkyl, C 3 -C 8 -cycloal- kyl, C3-C8-halocycloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkynyl, C2-C6-haloalky- nyl;
  • R 1 1 is halogen, CN, N 3 , NO 2 , SCN, SF 5 , Ci-Cio-alkyl, C 3 -C8-cycloalkyl, C 2 -Cio-alkenyl, C 2 -C 10 - alkynyl, or
  • C 3 -C 8 -cycloalkyl phenyl, benzyl, pyridyl, phenoxy; and a 3-, 4-, 5- or 6-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members;
  • W02009/063910 describes asymmetric syntheses of some isooxazoline compounds of for mula I by using cinchona alkaloid-based phase-transfer catalysts. The processes require rela tively high catalyst loadings and yield enantiomeric excesses of formula I compounds which still leave room for improvement.
  • Objective task for the invention therefore is providing an economical, industrially applicable manufacturing process for optically enriched compounds of formula I. This task is achieved by the process defined in the outset.
  • the presence of a catalyst III as defined herein in the reaction of compound II ensures a quick and effective transformation at moderate temperatures.
  • this catalyst is used in asymmetric oxa-Michael addition of hydroxyl amine with an enone to enantioselectively form a C-0 bond.
  • the process yields formula I compounds in good yield with at least 75% ee by using low catalyst loadings.
  • reaction of an enone of formula II, wherein the variables have the meanings given in the outset, with hydroxyl amine or its salt is usually carried out at temperatures of from -30°C to 35°C, preferably from -10°C to 0°C, in an inert solvent, in the presence of a catalyst of formula III.
  • the enone of formula II is used preferably as E-isomer. It corresponds to formula II.
  • the enone of formula II is used as Z-isomer. It corresponds to formula II.Z.
  • Suitable solvents are preferably water immiscible solvents, such as aliphatic hydrocarbons such as pentane, hexane, cyclohexane, and petrol ether, aromatic hydrocarbons such as tolu ene, 0-, m-, and p-xylene, halogenated hydrocarbons such as methylene chloride, dichloro- ethane, and chloroform, ethers such as diethylether, diisopropylether, tert.-butylmethylether (MTBE), anisole, and ketones such as methyl ethyl ketone, diethyl ketone, and tert.-butyl methyl ketone, alcohols such as n-butanol, preferably halogenated hydrocarbons such as methylene chloride, dichloroethane, and chloroform. It is also possible to use mixtures of the solvents men tioned.
  • aliphatic hydrocarbons such as pen
  • Suitable bases are in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as LiOH, NaOH, KOH and Ca(OH)2, alkali metal and alkaline earth metal oxides, such as LhO, Na 2 0, CaO, and MgO, and alkaline earth metal carbonates, such as U2CO3, Na 2 CC> 3 , K2CO3 and CaCCh, and also alkali metal bicarbonates, such as NaHCCh, moreover organic bases, e.g.
  • alkali metal and alkaline earth metal hydroxides such as LiOH, NaOH, KOH and Ca(OH)2
  • alkali metal and alkaline earth metal oxides such as LhO, Na 2 0, CaO, and MgO
  • alkaline earth metal carbonates such as U2CO3, Na 2 CC> 3 , K2CO3 and CaCCh
  • alkali metal bicarbonates such as NaHCCh
  • organic bases e.g.
  • tertiary amines such as trimethylamine, triethylamine (NEt3), diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines, such as DBU (1,8-Diazabicy- clo(5.4.0)undec-7-ene) and DBN (1,5-Diazabicyclo[4.3.0]non-5-ene).
  • alkali metal and alkaline earth metal hydroxides such as LiOH, NaOH, KOH, and Ca(OH)2, such as NaOH, and KOH.
  • the bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts or in excess. Under certain conditions an excess up to 10 mol equivalents of base to compound II may be advantageous.
  • hydroxylamine is preferably used in the form of an aqueous solution, al ternatively as acid addition salt, such as halogenide or sulfate, preferably halogenide, particu larly as HCI addition salt.
  • Hydroxylamine is generally employed in equimolar amounts; however, it can also be used in excess. Under certain conditions an excess up to 10 mol equivalents of hydroxylamine to com pound II may be advantageous.
  • the catalyst III is generally employed in catalytic amounts; such as in 0.005 to 0.05 mol equiv alents, or 0.01 to 0.5 mol eq., preferably 0.01 to 0.2, particularly about 0.02 to 0.1 mol equiva lents of compound II.
  • the starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of hydroxyl amine, based on II.
  • Compounds III can be prepared in accordance with the literature cited and US 9,126,995.
  • reaction mixtures are worked up in a customary manner, for example by mixing with wa ter, separating the phases and, if appropriate, chromatographic purification of the crude prod ucts.
  • Some of the intermediates and end products are obtained in the form of colourless or slightly brownish viscous oils which are purified or freed from volatile components under reduced pressure and at moderately elevated temperature. If the intermediates and end prod ucts are obtained as solids, purification can also be carried out by recrystallization or digestion.
  • the organic moieties mentioned in the above definitions of the variables are - like the term hal ogen - collective terms for individual listings of the individual group members.
  • the prefix C n -C m indicates in each case the possible number of carbon atoms in the group.
  • halogen denotes in each case fluorine, bromine, chlorine, or iodine, in particular flu orine, chlorine, or bromine.
  • alkyl as used herein and in the alkyl moieties of alkylamino, alkylcarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl and alkoxyalkyl denotes in each case a straight-chain or branched al kyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, prefer ably 1 to 4 carbon atoms, more preferably from 1 to 3 carbon atoms.
  • alkyl group examples include methyl (“Me”), ethyl (“Et”), n-propyl, iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl (“ ‘Bu”), n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl,
  • haloalkyl as used herein and in the haloalkyl moieties of haloalkylcarbonyl, haloalk- oxycarbonyl, haloalkylthio, haloalkylsulfonyl, haloalkylsulfinyl, haloalkoxy and haloalkoxyalkyl, denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 car bon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms.
  • Preferred haloalkyl moieties are selected from CrC4-haloalkyl, more preferably from CrC3-haloalkyl or CrC2-haloalkyl, in particular from Ci-C2-fluoroalkyl such as fluoromethyl, difluoromethyl, trifluo- romethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, and the like.
  • alkoxy denotes in each case a straight-chain or branched alkyl group which is bonded via an oxygen atom and has usually from 1 to 10 carbon atoms, fre quently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms.
  • alkoxy group examples are methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, 2-butyloxy, iso-butyloxy, tert.-butyloxy, and the like.
  • alkoxyalkyl refers to alkyl usually comprising 1 to 10, frequently 1 to 4, preferably 1 to 2 carbon atoms, wherein 1 carbon atom carries an alkoxy radical usually com prising 1 to 4, preferably 1 or 2 carbon atoms as defined above. Examples are CH2OCH3, CH2- OC2H5, 2-(methoxy)ethyl, and 2-(ethoxy)ethyl.
  • haloalkoxy denotes in each case a straight-chain or branched alk oxy group having from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms, in particular fluorine atoms.
  • Preferred haloalkoxy moieties include C1-C4- haloalkoxy, in particular Ci-C2-fluoroalkoxy, such as fluoromethoxy, difluoromethoxy, trifluoro- methoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-flu- oroethoxy, 2-chloro-2,2-difluoro-ethoxy, 2,2dichloro-2-fluorethoxy, 2,2,2-trichloroethoxy, penta- fluoroethoxy and the like.
  • Ci-C2-fluoroalkoxy such as fluoromethoxy, difluoromethoxy, trifluoro- methoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-flu- oro
  • alkylthio (alkylsulfanyl: S-alkyl)
  • alkoxycarbonyl refers to an alkylcarbonyl group as defined above, which is bonded via an oxygen atom to the remainder of the molecule.
  • alkenyl denotes in each case a singly unsaturated hydrocarbon rad ical having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. vinyl, allyl (2- propen-1-yl), 1 -propen-1 -yl, 2-propen-2-yl, methallyl (2-methylprop-2-en-1-yl), 2-buten-1-yl, 3- buten-1-yl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl, 2-ethylprop-2-en- 1 -yl and the like.
  • haloalkenyl refers to an alkenyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms.
  • alkynyl denotes in each case a singly unsaturated hydrocarbon rad ical having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. ethynyl, pro- pargyl (2-propyn-1-yl), 1-propyn-1-yl, 1-methylprop-2-yn-1-yl), 2-butyn-1-yl, 3-butyn-1-yl, 1-pen- tyn-1-yl, 3-pentyn-1-yl, 4-pentyn-1-yl, 1 -methyl but-2-yn-1-yl, 1-ethylprop-2-yn-1-yl and the like.
  • cycloalkyl as used herein and in the cycloalkyl moieties of cycloalkoxy and cycloal- kylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 or from 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl , cyclooctyl, cyclononyl, and cyclodecyl, or cyclopropyl (C-C 3 H5), cyclobutyl (C-C4H7), cyclopentyl (C-C5H 9 ), and cyclohexyl (c-CeHn).
  • halocycloalkyl as used herein and in the halocycloalkyl moieties of halocycloalkoxy and halocycloalkylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 C atoms or 3 to 6 C atoms, wherein at least one, e.g. 1, 2, 3, 4 or 5 of the hydrogen atoms, are replaced by halogen, in particular by fluorine or chlorine.
  • Examples are 1- and 2-fluo- rocyclopropyl, 1,2-, 2,2- and 2,3-difluorocyclopropyl, 1,2,2-trifluorocyclopropyl, 2,2,3,3-tetrafluo- rocyclpropyl, 1- and 2-chlorocyclopropyl, 1,2-, 2,2- and 2,3-dichlorocyclopropyl, 1,2,2-trichloro- cyclopropyl, 2,2,3,3-tetrachlorocyclpropyl, 1-,2- and 3-fluorocyclopentyl, 1,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-difluorocyclopentyl, 1-,2- and 3-chlorocyclopentyl, 1,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-dichlo- rocyclopentyl, and the like.
  • cycloalkenyl as used herein and in the cycloalkenyl moieties of cycloalkenyloxy and cycloalkenylthio denotes in each case a monocyclic singly unsaturated non-aromatic radical ha ving usually from 3 to 10, e.g. 3 or 4 or from 5 to 10 carbon atoms, preferably from 3- to 8 car bon atoms.
  • exemplary cycloalkenyl groups include cyclopropenyl, cycloheptenyl or cycloocte- nyl.
  • the term “carbocycle” or “carbocyclyl” includes in general a 3- to 12-membered, preferably a 3- to 8-membered or a 5- to 8-membered, more preferably a 5- or 6-membered mono-cyclic, non-aromatic ring comprising 3 to 12, preferably 3 to 8 or 5 to 8, more preferably 5 or 6 carbon atoms.
  • the term “carbocycle” covers cycloalkyl and cycloalkenyl groups as defined above.
  • heterocycle or “heterocyclyl” includes in general 3- to 12-membered, preferably 5- or 6-membered, in particular 6-membered monocyclic heterocyclic non-aromatic radicals.
  • the heterocyclic non-aromatic radicals usually comprise 1, 2 or 3 heteroatoms selected from N, O and S as ring members, wherein S-atoms as ring members may be present as S, SO or SO2.
  • heterocyclic radicals comprise saturated or unsaturated, non-aromatic heterocyclic rings, such as 2- and 3-azetidinyl, 2- and 3-oxetanyl, 2- and 3-thietanyl, 2- and 3-thietanyl-S- oxid (S-oxothietanyl), 2- and 3-thietanyl-S-dioxid (S-dioxothietanyl), 2- and 3-pyrrolidinyl, 2- and 3-tetrahydrofuranyl, 1,3-dioxolan-2-yl, thiolan-2-yl, S-oxothiolan-2-yl, S-dioxothiolan-2-yl, 4- and 5-oxazolidinyl, 1,3-dioxan-2-yl, 1- and 3-thiopyran-2-yl, S-oxothiopyranyl, and S-dioxothiopyra- nyl.
  • heteroaryl includes monocyclic 5- or 6-membered heteroaromatic radicals comprising as ring members 1 , 2, or 3 heteroatoms selected from N, O and S.
  • 5- or 6-mem- bered heteroaromatic radicals include pyridyl, i.e. 2-, 3-, and 4-pyridyl, pyrimidinyl, i.e. 2-, 4- and 5-pyrimidinyl, pyrazinyl, pyridazinyl, i.e. 3- and 4-pyridazinyl, thienyl, i.e. 2- and 3-thienyl, furyl, i.e. 2- and 3-furyl, pyrrolyl, i.e.
  • the particularly preferred embodiments of the intermediates cor respond to those of the compounds of the formula I.
  • variables of the compounds of the formula I have the following meanings, these meanings, both on their own and in combination with one another, being par ticular embodiments of the compounds of formula I.
  • R 1 is preferably fluoromethyl, in particular CF 3 .
  • R 2a is selected from
  • R 2b and R 2c are independently selected from H, F, Cl, Br, and OCF 3 .
  • substituents in group P are se lected from halogen, such as Cl and F.
  • Preferred embodiments of the invention are each one of the following combinations of R 2a , R 2b , and R 2c wherein each line of Table A denotes a substitution pattern of the phenyl ring P bearing the R 2a , R 2b , and R 2c moieties.
  • Groups A-8, A-9, and A-11 are more preferred patterns in formula I and its sub formulae com pounds. A-11 is particularly preferred.
  • R 3 is H, halogen, or CH 3 .
  • G 1 and G 2 represent each CR 3 , wherein R 3 is H, halogen, or C1-C4- alkyl, particularly G 1 is CH and G 2 is C-CI, or C-CH 3 .
  • G 1 and G 2 represent each CR 3 , wherein the two R 3 form a five- or sixmembered saturated carbocyclic ring, or a dihydrofurane.
  • W represents O.
  • the catalyst III is used preferably in an amount of 0.1-50 mol%, more preferred in 0.5-5 mol%, particularly in 1-5 mol% relative to formula II compounds.
  • the nature of the counteranion X in formula III catalyst is of minor importance. For practical reasons it is usually selected from halogen (preferably Cl, Br), BF4, PF 6 , Ci-Cio-alkylsulfonate, benzenesulfonate, or methylbenzenesulfonate.
  • Preferred III is used as bromide and chloride, mesylate, and tosylate. Particularly preferred are bromide and chloride.
  • Preferably p and q are both 0. in another embodiment index p is 1 or 2, and q is 0 or 1.
  • Substituents R a and R b are preferably positioned in 2 and/or 7, or in 3 and/or 6 positions.
  • R a and R b are preferably halogen, CN, CrC 3 -alkyl, or CrC 3 -alkoxy, particularly CH 3 , OCH 3 , or halogen such as Cl or F.
  • catalysts of formula III wherein the substitution of the acridin group have the meanings as shown in Table III.1, wherein each compound corresponds to one line.
  • bromide (lll-1-Br) and chloride (III-1-CI) of 111-1 are preferred embodiments.
  • R 5 is H or CH 3
  • R 6 is H, CrC 6 -alkyl, C2-C6-alkenyl, which groups are unsubstituted or substituted with one or more same or different R 8 , wherein R 8 is as defined and preferred above.
  • R 5 is preferably H or CH 3
  • R 6 is preferably H, CrC 6 -alkyl, Ci- C2-alkoxy-CrC2-alkyl, or C2-C6-alkenyl.
  • Table 1 Compounds of formula I.A in which R 2a , R 2b , and R 2c correspond to A-8, R 5 is H and R 6 for a compound correspond in each case to one row of Table B
  • Table 2 Compounds of formula I.A in which R 2a , R 2b , and R 2c correspond to A-9, R 5 is H and R 6 for a compound correspond in each case to one row of Table B
  • Table 3 Compounds of formula I.A in which R 2a , R 2b , and R 2c correspond to A-11, R 5 is H and R 6 for a compound correspond in each case to one row of Table B Table B
  • the process yields in formula I compounds which obtained from the raw reaction mixture have an ee of at least 80%, more preferably at least 85% ee. Further enrichment of the S-enantiomer can be achieved by following recrystallisation.
  • HPLC-MS high performance liquid chromatography-coupled mass spectrometry
  • HPLC Method A determination chemical purity of compounds: Shimadzu LC2010, Column: Waters XBridge C18, 150mm*4.6mm ID*5p; Mobile Phase: A: 0.1% trifluoroacetic acid (TFA) in water; B: 0.1% TFA in acetonitrile; Temperature: 40°C; Gradient: 10%B to 100%B in 5min; 100%B for 2mins; 10%B for 3min; Flow: 1 ,4ml/min; PDA detector MaxPlot (220nm to 400nm). Sample Preparation: In acetonitrile and water
  • HPLC Method B determination of enantiomeric purity of compounds: Shimadzu LC2010; CHIRALPAK AD-RH ,150mm*4.6mm*5p.
  • Mobile Phase A: 0.1% TFA in Water; B: 0.1% TFA in acetonitrile; Temperature: 40°C; Gradient: 65%B for 12mins; 100%B for 1min; 35%B for 7mins; Flow: 1 ,4 ml/min; PDA detector at 265nm. Sample Preparation: In acetonitrile and water.
  • Example II N-[[4-[(E )-3-(3,5-dichloro-4-fluoro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2,3-dihy- drobenzofuran-7-yl]methyl]thietane-3-carboxamide
  • N-[(4-acetyl-2,3-dihydrobenzofuran-7-yl)methyl]thietane-3-carbox- amide and 2.8g CS2CO3 in 16mL toluene and 16ml_ trifluorotoluene at 115°C was added 3.0g 1-(3,5-dichloro-4-fluoro-phenyl)-2,2,2-trifluoro-ethanone dropwise over 2 hours.
  • the reaction was then heated at 115°C for an additional 18 hours, then cooled to 20-25°C and concentrated in vacuo to afford a brown solid.
  • the solid was slurried in water and stirred vigorously for 1 hour, cooled to 0°C, and filtered.
  • the filtercake was then triturated with 25ml_ MTBE, filtered, and the filtercake then dried in a vacuum oven at 50°C to afford the title compound as a beige solid (2.77g, 69% yield).
  • Example 1 N-[[4-[(5S)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2, 3-dihydro- benzofuran-7-yl]methyl]propanamide [I.A-1]
  • a round bottom glass flask was charged with 1g (1eq) of N-[[4-[(E)-3-(3,5-dichlorophenyl)- 4,4,4-trifluoro-but-2-enoyl]-2,3-dihydrobenzofuran-7-yl]methyl]propanamide in 20 ml of chloro form and the reaction mass was cooled to -10°C; then to this solution was added 0.127g (0.05eq) (R)-[1-(acridin-9-ylmethyl)-5-vinyl-quinuclidin-1-ium-2-yl]-(6-methoxy-4-quinolyl)metha- nol bromide,

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Abstract

L'invention concerne un procédé de préparation de composés isoxazolines optiquement enrichis représentés par la formule (I), dans laquelle, les variables sont telles que définies dans la description, et l'énantiomère représenté ayant au moins 75% ee ; par addition d'oxo-Michael d'amine hydroxyle ou de son sel à une énone de formule (II), dans laquelle, les variables ont les significations données pour la formule (I), en présence d'un catalyseur de formule (III) et d'une base.
PCT/EP2021/061970 2020-05-13 2021-05-06 Procédé de préparation d'isoxazolines optiquement enrichies WO2021228673A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023152340A1 (fr) 2022-02-10 2023-08-17 Syngenta Crop Protection Ag Lutte contre les insectes, les acariens et les nématodes nuisibles

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WO2007105814A1 (fr) 2006-03-10 2007-09-20 Nissan Chemical Industries, Ltd. Compose isoxazoline substitue et agent antiparasite
WO2009063910A1 (fr) 2007-11-12 2009-05-22 Nissan Chemical Industries, Ltd. Procédé de synthèse catalytique asymétrique d'un composé d'isoxazoline optiquement actif
US20140350261A1 (en) * 2011-11-08 2014-11-27 Nissan Chemical Industries, Ltd. Method for catalytic asymmetric synthesis of optically active isoxazoline compound, and optically active isoxazoline compound

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WO2007105814A1 (fr) 2006-03-10 2007-09-20 Nissan Chemical Industries, Ltd. Compose isoxazoline substitue et agent antiparasite
WO2009063910A1 (fr) 2007-11-12 2009-05-22 Nissan Chemical Industries, Ltd. Procédé de synthèse catalytique asymétrique d'un composé d'isoxazoline optiquement actif
US20140350261A1 (en) * 2011-11-08 2014-11-27 Nissan Chemical Industries, Ltd. Method for catalytic asymmetric synthesis of optically active isoxazoline compound, and optically active isoxazoline compound
US9126995B2 (en) 2011-11-08 2015-09-08 Nissan Chemical Industries, Ltd. Method for catalytic asymmetric synthesis of optically active isoxazoline compound and optically active isoxazoline compound

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Publication number Priority date Publication date Assignee Title
WO2023152340A1 (fr) 2022-02-10 2023-08-17 Syngenta Crop Protection Ag Lutte contre les insectes, les acariens et les nématodes nuisibles

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