Sodium Methoxide → 4-Fluoro-2-(methoxymethyl)benzonitrile

HRID 505696Notes

Reaction equation

HRID 505696 reaction equation
Br[CH2:2][C:3]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:4]=1[C:5]#[N:6].[CH3:12][O-:13].[Na+]>CO>[F:11][C:9]1[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[C:3]([CH2:2][O:13][CH3:12])[CH:10]=1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 219849902-(Bromomethyl)-4-fluorobenzonitrile

Product 1

HCID 594293094-Fluoro-2-(methoxymethyl)benzonitrileYield 28.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-(bromomethyl)-4-fluorobenzonitrile (501 mg, 2.3 mmol) in methanol (5 mL) was treated with sodium methoxide (5.6 mL of 0.5 M solution in methanol, 2.81 mmol) and stirred for 1 hour at room temperature then heated to 55° C. for 2 hours. The mixture was cooled to room temperature, condensed to dryness and directly purified by normal phase flash column chromatography on a 20 g silica gel column (5-60% ethyl acetate/hexanes gradient). Pure fractions were pooled and concentrated in vacuo to yield 4-fluoro-2-(methoxymethyl)benzonitrile (110 mg, 0.66 mmol, 28% yield) as an oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.97 (dd, J=8.46, 5.50 Hz, 1H), 7.46 (dd, J=9.53, 2.55 Hz, 1H), 7.39 (td, J=8.59, 2.69 Hz, 1H), 4.58 (s, 2H), 3.37 (s, 3H).

Workup

  1. temperaturethen heated to 55° C. for 2 hours
  2. temperatureThe mixture was cooled to room temperature
  3. customcondensed to dryness
  4. customdirectly purified by normal phase flash column chromatography on a 20 g silica gel column (5-60% ethyl acetate/hexanes gradient)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-854480462fd24f6090a96873b3be4fe1
Source dataset
uspto-grants-2010_08
Patent number
US07781428B2

Reaction notes

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