反应详情

4-Iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (16.0 g, 64.3 mmol), 4-fluorophenylboronic acid (26.8 g, 193 mmol, Aldrich), copper(II) acetate (23.4 g, 129 mmol, Aldrich), and myristic acid (58.7 g, 257 mmol, Aldrich) were stirred together in 800 mL of toluene. To this solution was added 2,6-lutidine (60 mL, 514 mmol, Aldrich) and the reaction was stirred vigorously for 1 day. An additional 5 g of 4-fluorophenylboronic acid was added and the reaction was stirred vigorously for an additional 3 days. The reaction mixture was concentrated in vacuo and the resulting material was suspended in 10% methanol/ethyl acetate. Celite® was added and the mixture was stirred for 5 minutes. Next the mixture was filtered through a plug of Celite®, concentrated in vacuo, and the resulting material was suspended in ethyl acetate and water. The mixture was filtered through Celite® again to remove additional copper that had precipitated out, washing well with ethyl acetate. The filtrate was washed with 1N aqueous HCl, dried over sodium sulfate, filtered, and concentrated under vacuum. The resulting solid was triturated with ethyl acetate to yield 9.25 g (42%) of 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde as a yellow solid. The filtrate was concentrated in vacuo and the remaining solid was triturated again with ethyl acetate to yield an additional 5.75 g (68% total yield) of the desired product as a yellow solid. 1H NMR (DMSO-d6) δ 9.57 (s, 1H), 7.68 (d, 1H, J=7.2 Hz), 7.58-7.54 (m, 2H), 7.40 (t, 2H, J=8.8 Hz), 7.02 (d, 1H, J=7.2 Hz); MS (ESI+) m/z 344.13 (M+H)+.

1. stirringthe reaction was stirred vigorously for an additional 3 days
2. concentrationThe reaction mixture was concentrated in vacuo
3. additionCelite® was added
4. stirringthe mixture was stirred for 5 minutes
5. filtrationNext the mixture was filtered through a plug of Celite®
6. concentrationconcentrated in vacuo
7. filtrationThe mixture was filtered through Celite® again
8. customto remove additional copper that
9. customhad precipitated out
10. washwashing well with ethyl acetate
11. washThe filtrate was washed with 1N aqueous HCl
12. dry with materialdried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated under vacuum
15. customThe resulting solid was triturated with ethyl acetate