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

HRID 42720

Reaction equation

HRID 42720 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 and then 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, and 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
  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
  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-8810de413a5d48379127726abb1b4c20
Source dataset
uspto-grants-2013_09
Patent number
US08536200B2

Linked notes

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