Picolinic acid → 3-(4-(3-(1,1-Difluoroethyl)phenoxy)phenyl)pyridin-2-amine

HRID 1748016Notes

Reaction equation

HRID 1748016 reaction equation
N1C=CC=CC=1C(O)=O.[NH2:10][C:11]1[C:16]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)=[CH:15][CH:14]=[CH:13][N:12]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[CH3:40])[CH:34]=1>[Cu]I.CS(C)=O>[F:41][C:39]([C:35]1[CH:34]=[C:33]([CH:38]=[CH:37][CH:36]=1)[O:23][C:20]1[CH:21]=[CH:22][C:17]([C:16]2[C:11]([NH2:10])=[N:12][CH:13]=[CH:14][CH:15]=2)=[CH:18][CH:19]=1)([F:42])[CH3:40]

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 62657Potassium Phosphate, TribasicHCID 222401211-Bromo-3-(1,1-difluoroethyl)benzeneHCID 667484774-(2-Aminopyridin-3-yl)phenol

Product 1

HCID 667480523-(4-(3-(1,1-Difluoroethyl)phenoxy)phenyl)pyridin-2-amineYield 56.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

Copper(I) iodide (102 mg) was added to a mixture of picolinic acid (66.1 mg), 4-(2-aminopyridin-3-yl)phenol (500 mg), tripotassium phosphate (1710 mg), 1-bromo-3-(1,1-difluoroethyl)benzene (712 mg) and DMSO (8 mL). The mixture was stirred at 130° C. under nitrogen for 10 hr. Activated carbon was added and the insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc). Silica-gel was added to the filtrate and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane) and concentrated. The residue was purified by column chromatography (silica gel, eluted with EtOAc in hexane) to give the title compound (499 mg) as pale yellow oil.

Workup

  1. additionActivated carbon was added
  2. customthe insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc)
  3. additionSilica-gel was added to the filtrate
  4. customthe volatiles were removed in vacuo
  5. customwas purified by column chromatography (NH-silica gel, eluted with EtOAc in hexane)
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (silica gel, eluted with EtOAc in hexane)

Sources & evidence

ORD record
ord-19d01a53100a4be797d091285b9ee812
Source dataset
uspto-grants-2015_10
Patent number
US09150591B2

Reaction notes

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