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

HRID 1472607Notes

Reaction equation

HRID 1472607 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

A mixture of 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) in toluene (700 mL) was treated with 2,6-lutidine (45 mL, 385.5 mmol) and stirred vigorously at RT 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 to dryness, suspended in 10% MeOH/EtOAc and the solids removed via filtration through diatomaceous earth. The filtrate was concentrated to dryness, the residue treated with EtOAc and water and again filtered through diatomaceous earth. The filtrate was washed with 1N HCl, dried over Na2SO4 and concentrated to dryness. The material was treated with EtOAc and the resulting solid was collected via filtration to afford 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (8.0 g, 42%) as a yellow solid.

Workup

  1. stirringthe reaction was stirred vigorously for an additional 3 days
  2. concentrationThe reaction mixture was concentrated to dryness
  3. customthe solids removed via filtration through diatomaceous earth
  4. concentrationThe filtrate was concentrated to dryness
  5. additionthe residue treated with EtOAc and water
  6. filtrationagain filtered through diatomaceous earth
  7. washThe filtrate was washed with 1N HCl
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated to dryness
  10. additionThe material was treated with EtOAc
  11. filtrationthe resulting solid was collected via filtration

Sources & evidence

ORD record
ord-834d5716a8db486ab00ded6a9293b6a0
Source dataset
uspto-grants-2015_04
Patent number
US09012635B2

Reaction notes

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