Potassium Carbonate → HCID 59632142, compound

HRID 2369099Notes

Reaction equation

HRID 2369099 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]([F:24])([F:23])[F:22])[CH:9]=2)=[C:4]([Cl:25])[CH:3]=1.[CH3:26][O:27][C:28]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)=[O:29].C([O-])([O-])=O.[K+].[K+]>COCCOC.CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:25][C:4]1[CH:3]=[C:2]([C:34]2[CH:33]=[CH:32][CH:31]=[C:30]([C:28]([O:27][CH3:26])=[O:29])[CH:35]=2)[CH:7]=[CH:6][C:5]=1[C:8]1[N:12]([C:13]2[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:20])[N:11]=[C:10]([C:21]([F:24])([F:23])[F:22])[CH:9]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27347143-(Methoxycarbonyl)benzeneboronic acidHCID 59633411HCID 59633411, compound

Product 1

HCID 59632142HCID 59632142, compoundYield 88.2%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(4-bromo-2-chlorophenyl)-1-(2,6-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazole (3.55 g, 7.55 mmol) and 3-(methoxycarbonyl)phenylboronic acid (1.77 g, 9.83 mmol) in 1,2-dimethoxyethane (36 mL) was added K2CO3 (3.126 g, 22.65 mmol) and H2O (4 mL). The resulting biphasic suspension was stirred at ambient temperature and sparged with nitrogen for 10 minutes. The reaction was then treated with dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (600 mg, 0.734 mmol) and heated to 80° C. in an oil bath. The reaction was heated at 80° C. for 10 hours and then allowed to cool to ambient temperature. The cooled reaction mixture was diluted with EtOAc and H2O. The aqueous layer was extracted with EtOAc (3×). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated to afford crude product as a dark oil. The crude product was purified by flash-column chromatography eluting with a gradient from 0% to 40% EtOAc/hexane to afford methyl 3′-chloro-4′-(1-(2,6-dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)biphenyl-3-carboxylate (3.50 g, 88% yield) solid. MS(ES): 525 [M+H]+.

Workup

  1. customsparged with nitrogen for 10 minutes
  2. temperatureheated to 80° C. in an oil bath
  3. temperatureThe reaction was heated at 80° C. for 10 hours
  4. temperatureto cool to ambient temperature
  5. customThe cooled reaction mixture
  6. extractionThe aqueous layer was extracted with EtOAc (3×)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford crude product as a dark oil
  12. customThe crude product was purified by flash-column chromatography
  13. washeluting with a gradient from 0% to 40% EtOAc/hexane

Sources & evidence

ORD record
ord-1f6653e9650141939c4d4fe265fb03a0
Source dataset
uspto-grants-2014_04
Patent number
US08703805B2

Reaction notes

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