4-Bromophenol → 4-(Pyridin-2-ylamino)phenol

HRID 473612Notes

Reaction equation

HRID 473612 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[NH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[NH:9][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 78084-BromophenolHCID 104392-AminopyridineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxide

Product 1

HCID 212625714-(Pyridin-2-ylamino)phenol

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

To a microwave reaction vessel was added 4-bromophenol (5.5773 mL, 59.317 mmol), 2-aminopyridine (5.5942 g, 59.317 mmol), Pd2(dba)3 (1.3658 g, 1.4829 mmol), 2-di-t-butylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (2.5346 g, 5.9317 mmol), and sodium tert-butoxide (10.0798 g, 118.63 mmol). The vessel was capped and flushed with argon. Toluene was added and the vessel was flushed with argon. The temperature was brought to 100° C. to stir overnight. The reaction was monitored by LCMS to completion. The solvent was evaporated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage™ SNAP cartridge (KP-Sil 340 g), eluting with a gradient of 1.5% to 6% methanol in DCM, to provide 4-(pyridin-2-ylamino)phenol. MS (ESI, pos. ion) m/z: 187.0 (M+1).

Workup

  1. customTo a microwave reaction vessel
  2. customThe vessel was capped
  3. customflushed with argon
  4. additionToluene was added
  5. customthe vessel was flushed with argon
  6. customwas brought to 100° C.
  7. customThe solvent was evaporated
  8. customchromatographed through a Biotage™ SNAP cartridge (KP-Sil 340 g)
  9. washeluting with a gradient of 1.5% to 6% methanol in DCM

Sources & evidence

ORD record
ord-7d59ac7902944e7c996785746d96ef62
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

Loading…