8-Hydroxyquinoline → 2-Oxo-1-(4-(trifluoromethoxy)phenyl)-1,2-dihydropyridine-3-carbaldehyde

HRID 874685Notes

Reaction equation

HRID 874685 reaction equation
[O:1]=[C:2]1[C:7]([CH:8]=[O:9])=[CH:6][CH:5]=[CH:4][NH:3]1.I[C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=1.OC1C=CC=C2C=1N=CC=C2.C(=O)([O-])[O-].[K+].[K+].[OH-].[NH4+]>[Cu](I)I.C(OCC)(=O)C.CS(C)=O>[O:1]=[C:2]1[C:7]([CH:8]=[O:9])=[CH:6][CH:5]=[CH:4][N:3]1[C:11]1[CH:12]=[CH:13][C:14]([O:17][C:18]([F:19])([F:20])[F:21])=[CH:15][CH:16]=1

Participants

9

Reactant 5

HCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 27772941-Iodo-4-(trifluoromethoxy)benzeneHCID 70621962-Oxo-1,2-dihydropyridine-3-carbaldehyde

Product 1

HCID 895362582-Oxo-1-(4-(trifluoromethoxy)phenyl)-1,2-dihydropyridine-3-carbaldehydeYield 20%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

2-oxo-1,2-dihydropyridine-3-carbaldehyde 1-1 (200 mg, 1.63 mmol), 1-iodo-4-(trifluoromethoxy)benzene 2-1 (562 mg, 1.95 mmol), 8-hydroxyquinoline (47.2 mg, 0.324 mmol), copper iodide (61.9 mg, 0.324 mmol), and potassium carbonate (303 mg, 2.19 mmol) were combined in a round bottom flask with DMSO (3.5 mL) under a nitrogen atmosphere and heated to 130° C. for 21 h. The reaction was cooled to room temperature and poured into a mixture of 10% aq. ammonium hydroxide and ethyl acetate. The resultant mixture was filtered through a pad of Celite and washed with ethyl acetate three times. The layers were separated with the aqueous portion being back extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo. Purification by flash column chromatography on silica gel (0-50% EtOAc in hexane) gave 92.0 mg (20%) of 2-2 as an off-white solid: 1H NMR (400 MHz, CDCl3) δ 10.34 (1H, d, J=0.8 Hz), 8.14 (1H, dd, J=6.9, 2.3 Hz), 7.65 (1H, dd, J=6.9, 2.3 Hz), 7.45 (2H, m), 7.38 (2H, m), 6.44 (1H, dt, J=0.8, 6.9 Hz); ESI-MS m/z 284 [C13H8F3NO3+H]+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationThe resultant mixture was filtered through a pad of Celite
  3. washwashed with ethyl acetate three times
  4. customThe layers were separated with the aqueous portion
  5. extractionbeing back extracted with ethyl acetate
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customPurification by flash column chromatography on silica gel (0-50% EtOAc in hexane)

Sources & evidence

ORD record
ord-6cb8b72c63b749d89dc1989389593684
Source dataset
uspto-grants-2015_03
Patent number
US08980916B2

Reaction notes

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