Cesium carbonate → 4-Chloro-4'-fluorobiphenyl-2-amine

HRID 922103Notes

Reaction equation

Br[C:2]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][C:3]=1[NH2:4].[F:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.O>[Cl:9][C:6]1[CH:5]=[C:3]([NH2:4])[C:2]([C:14]2[CH:15]=[CH:16][C:11]([F:10])=[CH:12][CH:13]=2)=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

2-Bromo-5-chloroaniline (CAS#823-57-4; 5 g), 4-fluorophenylboronic acid (3.56 g) and cesium carbonate (31.6 g) were combined in THF (70 ml) and water (35 ml). The mixture was degassed by bubbling argon through the solution. After addition of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (886 mg) the reaction mixture was stirred 1 h at 80° C. in a sealed tube. The reaction mixture was diluted with EtOAc, washed with water, dried over Na2SO4, evaporated and purified by chromatography (silica gel, 0% to 30% EtOAc in heptane). The product was finally bulb-to-bulb distilled at 0.3 mbar and 120-130° C. oven temperature to give the title compound (5.07 g) as a light yellow liquid.

Workup

customThe mixture was degassed
customby bubbling argon through the solution
additionAfter addition of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (886 mg) the reaction mixture
additionThe reaction mixture was diluted with EtOAc
washwashed with water
dry with materialdried over Na2SO4
customevaporated
custompurified by chromatography (silica gel, 0% to 30% EtOAc in heptane)
distillationdistilled at 0.3 mbar and 120-130° C. oven temperature

Sources & evidence

ORD record: ord-a8cc7465a1084d31ab2f57396ffd0cf5
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278918B2

Reaction notes

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