Potassium Carbonate → HCID 59632594, compound

HRID 2369082Notes

Reaction equation

HRID 2369082 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:21])[F:20])[N:11]=[C:10]([C:23]([OH:26])([CH3:25])[CH3:24])[CH:9]=2)=[CH:4][CH:3]=1.[CH3:27][S:28]([C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)(=[O:30])=[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]>[CH3:27][S:28]([C:31]1[CH:36]=[C:35]([C:2]2[CH:3]=[CH:4][C:5]([C:8]3[N:12]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[C:19]([F:22])([F:21])[F:20])[N:11]=[C:10]([C:23]([OH:26])([CH3:24])[CH3:25])[CH:9]=3)=[CH:6][CH:7]=2)[CH:34]=[CH:33][CH:32]=1)(=[O:30])=[O:29]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 59632563HCID 59632563, compound

Product 1

HCID 59632594HCID 59632594, compoundYield 90.3%

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 2-(5-(4-bromophenyl)-1-(2-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)propan-2-ol (115 mg, 0.27 mmol) and 3-(methylsulfonyl)phenylboronic acid (66 mg, 033 mmol) in 1,2-dimethoxyethane (1.5 mL) was added K2CO3 (110 mg, 0.80 mmol) and H2O (1.5 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 (11) dichloromethane adduct (15 mg, 18 μmol) and heated to 80° C. in an oil bath. The reaction was heated at 80° C. for three hours and then allowed to cool to ambient temperature overnight. 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 10% to 100% EtOAc/hexane to afford 2-(5-(3′-(methylsulfonyl)biphenyl-4-yl)-1-(2-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)propan-2-ol (122 mg, 90% yield) as an off-white powder. MS(ES): 501 [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 three hours
  4. temperatureto cool to ambient temperature overnight
  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 10% to 100% EtOAc/hexane

Sources & evidence

ORD record
ord-3ad7ae62d30c4f4faa3774492e5f2351
Source dataset
uspto-grants-2014_04
Patent number
US08703805B2

Reaction notes

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