Isopropyl iodide → 4-Fluoro-2-isopropoxy-1-nitrobenzene

HRID 1754420Notes

Reaction equation

HRID 1754420 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([OH:8])[CH:7]=1.I[CH:13]([CH3:15])[CH3:14].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([O:8][CH:13]([CH3:15])[CH3:14])[CH:7]=1

Participants

5

Reactant 3

HCID 6362Isopropyl iodideHCID 99375-Fluoro-2-nitrophenolHCID 11430Potassium Carbonate

Product 1

HCID 106318324-Fluoro-2-isopropoxy-1-nitrobenzeneYield 78%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 5-fluoro-2-nitrophenol (50.0 g, 318 mmol, 1 equiv), 2-iodopropane (96.0 mL, 955 mmol, 3 equiv), and K2CO3 (132.0 g, 955 mmol, 3 equiv) in acetone (1 L) was heated to reflux for ON. After cooling to RT, the solid was filtered-off and rinsed with DCM, then the filtrate was concentrated to dryness. The residue was taken in water, EtOAc, and 1N NaOH. The layers were separated, and the organic layer was washed with 1N NaOH 1×. The organic layer was dried over Na2SO4, filtered, and concentrated to dryness to provide 4-fluoro-2-isopropoxy-1-nitrobenzene (49.3 g, 78%) as a yellow-brown liquid that was used without further purification. 1H NMR (300 MHz; d6-DMSO) δ 7.91-7.96 (dd, 1H, J=6.3 Hz, 9.0 Hz), 7.31-7.35 (dd, 1H, J=2.4 Hz, 11 Hz), 6.88-6.95 (m, 1H), 4.77-4.89 (hep, 1H, J=6.0 Hz), 1.27-1.29 (d, 6H, J=6.0 Hz); 19F NMR (282 MHz; d6-DMSO) δ −102.4 (sextet); m/z=200 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for ON
  3. washrinsed with DCM
  4. concentrationthe filtrate was concentrated to dryness
  5. customThe layers were separated
  6. washthe organic layer was washed with 1N NaOH 1×
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-1f7aaa74416f4fbeb272c64e76116cec
Source dataset
uspto-grants-2015_10
Patent number
US09169249B2

Reaction notes

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