Pyridine, hydrofluoride (1:1) → 1-Fluoro-5-methoxy-2-methyl-4-nitrobenzene

HRID 2229553Notes

Reaction equation

HRID 2229553 reaction equation
C1C=CN=CC=1.[FH:7].[CH3:8][O:9][C:10]1[C:11]([N+:18]([O-:20])=[O:19])=[CH:12][C:13]([CH3:17])=[C:14](N)[CH:15]=1.N([O-])=O.[Na+]>N1C=CC=CC=1>[F:7][C:14]1[CH:15]=[C:10]([O:9][CH3:8])[C:11]([N+:18]([O-:20])=[O:19])=[CH:12][C:13]=1[CH3:17]

Participants

5

Reactant 3

HCID 64774Pyridine, hydrofluoride (1:1)HCID 6027265-Methoxy-2-methyl-4-nitroanilineHCID 23668193Sodium Nitrite

Product 1

HCID 184681411-Fluoro-5-methoxy-2-methyl-4-nitrobenzeneYield 76%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Under nitrogen in a nalgene bottle, a stirring solution of pyridine (17.1 mL, 3.2 M, −70° C.) was treated dropwise with HF-pyridine (51.91 mL). Next, 5-methoxy-2-methyl-4-nitro-phenylamine (10.0 g, 54.9 mmol) was added followed by sodium nitrite (6.4 g, 92.76 mmol). The dry ice/acetone bath was removed and the reaction was allowed to warm to room temperature. The solution was then heated at 60° C. for 2 h (or until nitrogen evolution stops.) After cooling to room temperature, the nalgene bottle was placed in an ice bath and 375 mL of water was slowly added to the solution. The resulting orange precipitate was collected by suction filtration and washed with 250 mL of water. Purification of the solid via silica gel flash chromatography (30% ethyl acetate in heptane) provided 1-fluoro-5-methoxy-2-methyl-4-nitro-benzene (7.69 g, 76%) as a light orange solid: mp 71-74°C. Rf 0.56 (30% ethyl acetate in heptane); 1H NMR (CDCl3, 300 MHz) δ 7.82 (d, J=7.5 Hz, 1H), 6.75 (d, J=10.5 Hz, 1H), 3.93 (s, 3H), 2.25 (d, J=2.1 Hz, 3H); ESI-LC/MS m/z calcd for C8H8FNO3: 185.1; Found 186.0 (M+1)+. Anal. calcd for C8H8FNO3: C, 51.90; H, 4.36. Found C, 52.11; H, 4.47.

Workup

  1. customThe dry ice/acetone bath was removed
  2. temperatureThe solution was then heated at 60° C. for 2 h (or until nitrogen evolution stops.)
  3. temperatureAfter cooling to room temperature
  4. customthe nalgene bottle was placed in an ice bath
  5. addition375 mL of water was slowly added to the solution
  6. filtrationThe resulting orange precipitate was collected by suction filtration
  7. washwashed with 250 mL of water
  8. customPurification of the solid via silica gel flash chromatography (30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-8a7fc15dc9464f54bb2d80152ab29ef4
Source dataset
uspto-grants-2002_07
Patent number
US06420426B1

Reaction notes

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