Sodium Carbonate → 5-Bromo-4-methyl-3-(3-trifluoromethyl-phenyl)-pyridin-2-ylamine

HRID 1497746Notes

Reaction equation

HRID 1497746 reaction equation
[Br:1][C:2]1[C:3]([CH3:10])=[C:4](I)[C:5]([NH2:8])=[N:6][CH:7]=1.[F:11][C:12]([F:23])([F:22])[C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[Br:1][C:2]1[C:3]([CH3:10])=[C:4]([C:17]2[CH:16]=[CH:15][CH:14]=[C:13]([C:12]([F:23])([F:22])[F:11])[CH:18]=2)[C:5]([NH2:8])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 401518975-Bromo-3-iodo-4-methylpyridin-2-amine

Product 1

HCID 867080865-Bromo-4-methyl-3-(3-trifluoromethyl-phenyl)-pyridin-2-ylamineYield 163.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

5-Bromo-3-iodo-4-methyl-pyridin-2-ylamine (20.0 g, 63.9 mmol) and 3-(trifluoromethyl)benzene boronic acid (12.73 g, 67.0 mmol) were mixed with sodium carbonate (2 M, 160 mL, 320 mmol), toluene (570 mL) and IMS (190 mL) and degassed. 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane (3.13 g, 36.83 mmol) was added and the reaction mixture was degassed again before heating to reflux for 2 hrs. A second reaction was carried on 1.08 times the scale. The two batches were combined and the solvent was removed in vacuo and the resulting mixture was partitioned between DCM and water. The organic phase was separated and was washed with water, dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography through a pad of silica, eluting with a gradient of 5-30% EtOAc in cyclohexane to give the title compound as a beige solid (34.6 g).

Workup

  1. customdegassed
  2. customthe reaction mixture was degassed again
  3. temperaturebefore heating
  4. temperatureto reflux for 2 hrs
  5. customA second reaction
  6. customthe solvent was removed in vacuo
  7. customthe resulting mixture was partitioned between DCM and water
  8. customThe organic phase was separated
  9. washwas washed with water
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe resultant residue was purified by flash chromatography through a pad of silica
  13. washeluting with a gradient of 5-30% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-4ea7ac58ca1345b0bad1e67c505c7470
Source dataset
uspto-grants-2015_12
Patent number
US09199984B2

Reaction notes

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