Potassium Phosphate, Tribasic → 4-Cyclopropyl-2-fluoro-3-trifluoromethylaniline

HRID 1270727Notes

Reaction equation

HRID 1270727 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[C:3]=1[C:10]([F:13])([F:12])[F:11].[CH:14]1(B(O)O)[CH2:16][CH2:15]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.CCOCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:14]1([C:2]2[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[C:3]=2[C:10]([F:13])([F:12])[F:11])[CH2:16][CH2:15]1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 536697144-Bromo-2-fluoro-3-(trifluoromethyl)aniline

Product 1

HCID 184515234-Cyclopropyl-2-fluoro-3-trifluoromethylaniline

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
90 °C

Procedure

4-Bromo-2-fluoro-3-trifluoromethylaniline (5.0 g, 19.4 mmol), cyclopropylboronic acid (2.16 g, 25.2 mmol), K3PO4 (14.4 g, 67.8 mmol) and tricyclohexyl phosphine (0.54 g, 1.9 mmol) are dissolved in toluene (80 mL) and water (4 mL). The solution is degassed with N2, heated to 90° C., and Pd(OAc)2 (0.22 g, 1.0 mmol) is added. The reaction is heated at 90° C. for 5 hours, cooled, diluted with Et2O, filtered, washed with brine, dried (Na2SO4) and concentrated in vacuo. The residue is purified by column chromatography (EtOAc/hexanes) to give 4-cyclopropyl-2-fluoro-3-trifluoromethylaniline.

Workup

  1. customThe solution is degassed with N2
  2. temperatureThe reaction is heated at 90° C. for 5 hours
  3. temperaturecooled
  4. filtrationfiltered
  5. washwashed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by column chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-1c0ddd803b684bd0b525042fea3dc808
Source dataset
uspto-grants-2007_04
Patent number
US07202364B2

Reaction notes

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