Methanol → 5-Fluoro-2,4-dimethoxybenzonitrile

HRID 2357120Notes

Reaction equation

HRID 2357120 reaction equation
[CH3:1][O-:2].[Na+].F[C:5]1[CH:12]=[C:11](F)[C:10]([F:14])=[CH:9][C:6]=1[C:7]#[N:8].[CH3:15][OH:16]>>[F:14][C:10]1[C:11]([O:16][CH3:15])=[CH:12][C:5]([O:2][CH3:1])=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

4

Reactant 3

HCID 887MethanolHCID 5938132,4,5-TrifluorobenzonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 593857025-Fluoro-2,4-dimethoxybenzonitrileYield 95%

Procedure

Sodium methoxide (25% wt in MeOH, 32 mL) was added dropwise to a solution of 2,4,5-trifluorobenzonitrile (10 g, 63.7 mmol) in MeOH (160 mL) under nitrogen at 0° C. The resulting reaction mixture was stirred at reflux for 48 h. The reaction was then quenched with 1 M citric acid and the MeOH was removed in vacuo. The residue was taken up in EtOAc, washed with brine, dried over Na2SO4, concentrated in vacuo and recrystallized from EtOAc/hexane to furnish the desired product in 95% yield (11 g). 1H NMR (300 MHz, CDCl3) δ 7.25 (d, 1H, J=10.2 Hz), 6.52 (d, 1H, J=6.8 Hz), 3.97 (s, 3H), 3.93 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 159.3, 159.2, 152.8, 152.6, 147.6, 144.4, 119.8, 119.5, 115.8, 115.7, 97.4, 97.3, 92.1, 92.0, 56.6, 56.5; 19F NMR (282 MHz, CDCl3) δ −143.4 (dd, 1 F); mass spectrum, calculated for C9H8FNO2 (MH+) 182.1, Found 182.1.

Workup

  1. customThe resulting reaction mixture
  2. temperatureat reflux for 48 h
  3. customThe reaction was then quenched with 1 M citric acid
  4. customthe MeOH was removed in vacuo
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customrecrystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-b764fb0b25924805b0e25cc2b5cd30bd
Source dataset
uspto-grants-2010_07
Patent number
US07759459B2

Reaction notes

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