Potassium Phosphate, Tribasic → 3-Cyclopropyl-4-fluoroaniline

HRID 19791

Reaction equation

HRID 19791 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=1[F:8].[CH:10]1(B(O)O)[CH2:12][CH2:11]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:10]1([C:2]2[CH:3]=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=2[F:8])[CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 27792863-Bromo-4-fluoroaniline

Product 1

HCID 574163033-Cyclopropyl-4-fluoroanilineYield 64%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-bromo-4-fluorophenylamine (synthesized as described in J. Org. Chem. 1981, 46, 2280-2286) (415 mg, 2.18 mmol), cyclopropyl boronic acid (244 mg, 2.84 mmol), potassium phosphate (1.62 g, 7.64 mmol), and tricyclohexyl phosphine (61 mg, 0.22 mmol) in toluene (10 ml) and water (0.5 ml) was added palladium acetate (25 mg, 0.11 mmol) and the reaction mixture was heated to 100° C. overnight. The mixture was then cooled to RT and diluted with water and extracted with ether. The organic phases were combined, washed with brine, dried (MgSO4), filtered and concentrated in vacuo to give a residue which was purified by flash column chromatography to give 3-cyclopropyl-4-fluorophenylamine (210 mg, 64%). MS (ISP) 152.2 (M+H)+.

Workup

  1. temperatureThe mixture was then cooled to RT
  2. extractionextracted with ether
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a residue which
  8. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-14b57bd0666e45aab253ce6c60b843fa
Source dataset
uspto-grants-2010_06
Patent number
US07745477B2

Linked notes

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