8-Hydroxyquinoline → 1-(4-Amino-3-fluorophenyl)pyridin-2-one

HRID 1987172Notes

Reaction equation

HRID 1987172 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[CH:3]=1.[OH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.[Cu]I>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([N:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]2=[O:10])=[CH:3][C:4]=1[F:9]

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 1230504-Bromo-2-fluoroanilineHCID 178516071HCID 178516071, compound

Product 1

HCID 221815481-(4-Amino-3-fluorophenyl)pyridin-2-one

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

4-Bromo-2-fluoroaniline (13.0 g; 68 mmol), 2-hydroxypyridine (9.11 g; 96 mmol), 8-hydroxyquinoline (1.5 g; 10 mmol) are dissolved under argon in DMSO (40 ml). To this solution K2CO3 (10.4 g; 75 mmol) and CuI (1.95 g; 10 mmol) are added and the resulting suspension is heavily stirred under argon at 150° C. for 18 h. The mixture is evaporated to dryness under reduced pressure and the final residue is chromatographed over silica gel (400 g) using dichloromethane/methanol as eluents. The obtained crude product is recrystallized with diethyl ether to yield an off-white solid. Yield: 2.80 g (20.0%), ESI-MS: m/z=205 [M+H]+

Workup

  1. customThe mixture is evaporated to dryness under reduced pressure
  2. customthe final residue is chromatographed over silica gel (400 g)
  3. customThe obtained crude product
  4. customis recrystallized with diethyl ether
  5. customto yield an off-white solid

Sources & evidence

ORD record
ord-c92fb226905a483c97c4efa45689d654
Source dataset
uspto-grants-2009_06
Patent number
US07550487B2

Reaction notes

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