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

HRID 874686Notes

Reaction equation

HRID 874686 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:12]=[C:13]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][C:18]2=[O:23])[CH:14]=[CH:15][CH:16]=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:15]1[CH:16]=[CH:11][CH:12]=[C:13]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][C:18]2=[O:23])[CH:14]=1

Participants

9

Reactant 5

HCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 70621962-Oxo-1,2-dihydropyridine-3-carbaldehydeHCID 581817424-(3-Iodophenyl)morpholin-3-one

Product 1

HCID 895362822-Oxo-1-(3-(3-oxomorpholino)phenyl)-1,2-dihydropyridine-3-carbaldehydeYield 25.2%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

30 mL microwave reaction vessel was flushed with nitrogen gas and charged with 2-oxo-1,2-dihydropyridine-3-carbaldehyde 1-1 (100 mg, 0.812 mmol), 4-(3-iodophenyl)morpholin-3-one 3-1 (296 mg, 0.974 mmol), 8-hydroxyquinoline (48.0 mg, 0.324 mmol), copper iodide (31.0 mg, 0.162 mmol), potassium carbonate (152 mg, 1.09 mmol) and DMSO (1.7 mL) under a nitrogen atmosphere. The resulting mixture was irradiated in a microwave apparatus (Biotage) at 150° C. for 15 minutes. 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 silica gel column chromatography (0-100% EtOAc in hexane) gave 61.0 mg (24%) of 3-2 as a light brown solid: 1H NMR (400 MHz, CDCl3) δ 10.33 (1H, d, J=0.4 Hz), 8.14 (1H, dd, J=6.8, 2.3 Hz), 7.27 (1H, dd, J=6.8, 2.3 Hz), 7.60 (1H, t, J=8.1 Hz), 7.53 (1H, t, J=2.1 Hz), 7.47 (1H, ddd, J=8.1, 2.1, 1.2 Hz), 7.32 (1H, ddd, J=8.1, 2.1, 1.2 Hz), 6.43 (1H, dt, J=6.8, 0.4 Hz), 4.34 (2H, br, s), 4.03-4.06 (2H, m), 3.84-3.86 (2H, m); ESI-MS m/z 299 [C16H14N2O4+H]+.

Workup

  1. custom30 mL microwave reaction vessel was flushed with nitrogen gas
  2. customThe resulting mixture was irradiated in a microwave apparatus (Biotage) at 150° C. for 15 minutes
  3. filtrationThe resultant mixture was filtered through a pad of Celite
  4. washwashed with ethyl acetate three times
  5. customThe layers were separated with the aqueous portion
  6. extractionbeing back extracted with ethyl acetate
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customPurification by silica gel column chromatography (0-100% EtOAc in hexane)

Sources & evidence

ORD record
ord-32a90bf0137d4f8bb6204f7d2721c1bc
Source dataset
uspto-grants-2015_03
Patent number
US08980916B2

Reaction notes

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