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

Participants

Reaction Steps

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]+.

Provenance & Evidence