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

HRID 1848710Notes

Reaction equation

HRID 1848710 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-methylpyridineYield 73.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

3-fluoro-4-nitrophenol (200.0 g, 1.27 mol) was added to a solution of 2-(chloromethyl)-5-methylpyridine hydrochloride (222 g, 1.25 mol), powdered potassium carbonate (383.6 g, 2.75 mol), potassium iodide (207 g, 1.25 mol), and acetonitrile (3.4 L). The resulting mixture was stirred at 60° Celsius for 2 h. The reaction was cooled to RT, concentrated to dryness and partitioned between H2O (1.5 L) and ethyl acetate (1.5 L). The organic layers were separated and the aqueous layer was extracted with ethyl acetate (1.0 L). The combined organic layers were washed with brine (1 L) then dried over magnesium sulfate, filtered, and concentrated to dryness. The crude solid was recrystallized from i-PrOH (1.5 L) at 70° Celsius. After cooling to 0° Celsius the solid was collected by filtration and rinsed with i-PrOH (2×200 mL) and heptanes (2×200 mL) to yield the title compound as a dark solid (242.0 g, 73.9%). MS (ESI): mass calcd. for C13H11FN2O3, 262.10; m/z found, 263.1 [M+H]+. 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. temperatureThe reaction was cooled to RT
  2. concentrationconcentrated to dryness
  3. custompartitioned between H2O (1.5 L) and ethyl acetate (1.5 L)
  4. customThe organic layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (1.0 L)
  6. washThe combined organic layers were washed with brine (1 L)
  7. dry with materialthen dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe crude solid was recrystallized from i-PrOH (1.5 L) at 70° Celsius
  11. temperatureAfter cooling to 0° Celsius the solid
  12. filtrationwas collected by filtration
  13. washrinsed with i-PrOH (2×200 mL) and heptanes (2×200 mL)

Sources & evidence

ORD record
ord-724a1fce1dae432bab2ad00bdb4d1f09
Source dataset
uspto-grants-2015_02
Patent number
US08952177B2

Reaction notes

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