Cesium carbonate → 4-Cyclopropyl-3,5-difluoroaniline

HRID 1411413Notes

Reaction equation

HRID 1411413 reaction equation
Br[C:2]1[C:8]([F:9])=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[F:10].C(=O)([O-])[O-].[Cs+].[Cs+].[CH:17]1([B-](F)(F)F)[CH2:19][CH2:18]1.[K]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.I.C12(P(C34CC5CC(CC(C5)C3)C4)CCCC)CC3CC(CC(C3)C1)C2.O.C1(C)C=CC=CC=1>[CH:17]1([C:2]2[C:8]([F:9])=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=2[F:10])[CH2:19][CH2:18]1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 27362604-Bromo-3,5-difluoroanilineHCID 5462222PotassiumHCID 16217981Cyclopropyltrifluoroborate

Product 1

HCID 666305064-Cyclopropyl-3,5-difluoroanilineYield 82%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 66629336Phosphine, butylbis(tricyclo(3.3.1.13,7)dec-1-yl)-, hydriodide (1:1)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a pressure tube was added 4-bromo-3,5-difluoroaniline (1.0 g, 4.8 mmol), cesium carbonate (4.7 g, 14.4 mmol), toluene (10 mL) and water (1 mL). The solution was de-gassed with N2 gas for 30 minutes, followed by the addition of cyclopropyltrifluoro-borate, potassium salt (0.8 g, 5.3 mmol), di(1-adamantyl)-n-butylphosphine hydroiodide (0.07 g, 0.14 mmol) and palladium(II) acetate (0.02 g, 0.096 mmol). De-gassing was continued for 5 minutes, the tube was sealed and heated at 100° C. for 18 hours. The cooled solution was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4), and filtered. The filtrate was treated with 3-mercaptopropyl silica gel for 1 hour. The mixture was filtered and concentrated to give crude product which was purified by flash chromatography (0-30% EtOAc/hexane) to give the title compound (0.67 g, 4.0 mmol, 82%).

Workup

  1. customThe solution was de-gassed with N2 gas for 30 minutes
  2. customDe-gassing
  3. customthe tube was sealed
  4. additionThe cooled solution was diluted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. additionThe filtrate was treated with 3-mercaptopropyl silica gel for 1 hour
  9. filtrationThe mixture was filtered
  10. concentrationconcentrated
  11. customto give crude product which
  12. customwas purified by flash chromatography (0-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-9e4d9da843e449fe9bdd8ae3aa784ffa
Source dataset
uspto-grants-2014_12
Patent number
US08921514B2

Reaction notes

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