2,6-Lutidine → 1-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde

HRID 1043042Notes

Reaction equation

HRID 1043042 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=1[CH:9]=[O:10].[F:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C(O)(=O)CCCCCCCCCCCCC.N1C(C)=CC=CC=1C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:11][C:12]1[CH:17]=[CH:16][C:15]([N:5]2[CH:6]=[CH:7][C:2]([I:1])=[C:3]([CH:9]=[O:10])[C:4]2=[O:8])=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 11005Myristic AcidHCID 2856454-Fluorophenylboronic acid2×HCID 184399262-Hydroxy-4-iodonicotinaldehyde

Product 1

HCID 252319761-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehydeYield 42%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 1140TolueneSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-d1d8d2d09fd348a299d1dffd2eda09ea
Source dataset
uspto-grants-2013_10
Patent number
US08558000B2

Reaction notes

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