Potassium Iodide → 2-((3-Fluoro-4-nitrophenoxy)methyl)-5-methylpyridine

HRID 1527719Notes

Reaction equation

HRID 1527719 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].Cl.Cl[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][N:16]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9])[O:11][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][N:16]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 5209483-Fluoro-4-nitrophenolHCID 233137952-(Chloromethyl)-5-methylpyridine hydrochloride

Product 1

HCID 904110842-((3-Fluoro-4-nitrophenoxy)methyl)-5-methylpyridine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a 3-neck, 1 L flask equipped with mechanical stirring, a nitrogen inlet, and temperature probe, 3-fluoro-4-nitrophenol (30 g, 191 mmol) was added to a suspension of 2-(chloromethyl)-5-methylpyridine hydrochloride (33.4 g, 187 mmol), potassium carbonate (57.5 g, 412 mmol), potassium iodide (31.1 g, 187 mmol), and acetonitrile (400 mL) and the mixture was then heated to 60° Celsius. After 3 hours the solvent was evaporated to dryness and the residue was partitioned between EtOAc and water and the organic layer was separated, dried, filtered and concentrated to dryness. To the resulting residue was added IPA (200 mL) and the mixture was heated to 70° Celsius where the suspension became homogeneous. The solution was allowed to cool to RT over 2 hours and placed in the freezer overnight. The solids were collected by filtration and were rinsed with IPA (100 mL) followed by heptanes (2×100 mL) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.44 (s, 1H), 8.16 (t, J=9.2, 1H), 7.76-7.62 (m, 1H), 7.45 (d, J=7.9, 1H), 7.30 (dd, J=13.7, 2.5, 1H), 7.07 (dd, J=9.3, 1.9, 1H), 5.30 (s, 2H), 2.31 (s, 3H).

Workup

  1. customAfter 3 hours the solvent was evaporated to dryness
  2. customthe residue was partitioned between EtOAc and water
  3. customthe organic layer was separated
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. additionTo the resulting residue was added IPA (200 mL)
  8. temperaturethe mixture was heated to 70° Celsius where the suspension
  9. temperatureto cool to RT over 2 hours
  10. customplaced in the freezer overnight
  11. filtrationThe solids were collected by filtration
  12. washwere rinsed with IPA (100 mL)

Sources & evidence

ORD record
ord-31bbae3f37c44031b53d0768fd8b7edf
Source dataset
uspto-grants-2015_07
Patent number
US09089569B2

Reaction notes

Loading…