Toluene → HCID 22228442, compound

HRID 1744694Notes

Reaction equation

HRID 1744694 reaction equation
[C:1]([N:5]1[CH2:10][C:9](OS(C(F)(F)F)(=O)=O)=[C:8]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[F:24][C:25]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=1B(O)O.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>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].C(O)C>[C:1]([N:5]1[CH2:10][C:9]([C:28]2[CH:27]=[CH:26][C:25]([F:24])=[CH:30][C:29]=2[F:31])=[C:8]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:7][CH2:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 22228438HCID 22228438, compound

Product 1

HCID 22228442HCID 22228442, compoundYield 60.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

The product of step D (5.05 g; 14.4 mmol), 2,4-difluorophenylboronic acid (2.85 g; 18.0 mmol) and [1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (0.589 g; 0.7 mmol) were combined and dissolved a 2:1 mixture of toluene:ethanol (54 mL). The reaction was heated to 80° C. followed by the dropwise addition of 2 M aqueous sodium carbonate over 10 min. The reaction was maintained at 80° C. for 2 h. The reaction was quenched with saturated aqueous sodium bicarbonate and the aqueous layer was extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), filtered concentrated in vacuo. The crude residue was purified on silica gel using a gradient elution (30%→40%→60% ethyl acetate/hexane) which furnished the title compound (2.8 g).

Workup

  1. dissolutiondissolved
  2. temperatureThe reaction was maintained at 80° C. for 2 h
  3. customThe reaction was quenched with saturated aqueous sodium bicarbonate
  4. extractionthe aqueous layer was extracted three times with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified on silica gel using
  10. washa gradient elution (30%→40%→60% ethyl acetate/hexane) which

Sources & evidence

ORD record
ord-5a8db05f4251496694eb99422c4aa7b0
Source dataset
uspto-grants-2006_03
Patent number
US07015235B2

Reaction notes

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