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

HRID 1050858Notes

Reaction equation

HRID 1050858 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 48.3%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 1140TolueneSolvent

Procedure

4-Iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (12.0 g, 48.3 mmol), 4-fluorophenylboronic acid (20.1 g, 144.7 mmol), copper(II) acetate (17.55 g, 96.75 mmol), and myristic acid (44 g, 193 mmol) were combined in toluene (700 mL), treated 2,6-lutidine (45 mL, 385 mmol), and stirred vigorously for 1 day. Additional 4-fluorophenylboronic acid (5 g) was added and the reaction was stirred vigorously for an additional 3 days. The reaction mixture was concentrated and then suspended in 10% methanol/EtOAc. Diatomaceous earth was added and the mixture was stirred for 5 minutes. The mixture was filtered through a plug of diatomaceous earth. The filtrate was concentrated, and suspended in EtOAc and water. The mixture was again filtered through diatomaceous earth, rinsing forward with EtOAc. The filtrate was washed with 1N HCl, dried over Na2SO4, and concentrated under vacuum. The resulting solid was triturated with EtOAc to yield 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (8.0 g, 42% yield) as a yellow solid.

Workup

  1. stirringthe reaction was stirred vigorously for an additional 3 days
  2. concentrationThe reaction mixture was concentrated
  3. additionDiatomaceous earth was added
  4. stirringthe mixture was stirred for 5 minutes
  5. filtrationThe mixture was filtered through a plug of diatomaceous earth
  6. concentrationThe filtrate was concentrated
  7. filtrationThe mixture was again filtered through diatomaceous earth
  8. washrinsing forward with EtOAc
  9. washThe filtrate was washed with 1N HCl
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated under vacuum
  12. customThe resulting solid was triturated with EtOAc

Sources & evidence

ORD record
ord-4d2ac344416948c2936c0c3b7ea401a4
Source dataset
uspto-grants-2016_07
Patent number
US09387202B2

Reaction notes

Loading…