Water → HCID 66891788, compound

HRID 253282Notes

Reaction equation

HRID 253282 reaction equation
Cl[CH2:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[C:5]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:4]=1[O:18][CH3:19].[C-:20]#[N:21].[K+].O>CN(C=O)C.[Cl-].[Na+].O>[F:9][C:7]1[CH:6]=[C:5]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:4]([O:18][CH3:19])=[C:3]([CH2:2][C:20]#[N:21])[CH:8]=1

Participants

6

Reactant 3

HCID 962WaterHCID 9032Potassium CyanideHCID 66891080HCID 66891080, compound

Product 1

HCID 66891788HCID 66891788, compoundYield 80.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-(chloromethyl)-5-fluoro-2-(methyloxy)-3-[(phenylmethyl)oxy]benzene (6.82 g, 24.3 mmol) in DMF (60 mL) was added potassium cyanide (3.2 g, 48.6 mmol), and the resulting mixture was stirred at 50° C. for 2 h 20 min before cooling to rt. Water and brine were added, and the resulting aqueous mixture was extracted with ethyl acetate. The organic phase was washed twice with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (80% hexanes, 20% ethyl acetate) to afford {5-fluoro-2-(methyloxy)-3-[(phenylmethyl)oxy]phenyl}acetonitrile (5.3 g, 19.5 mmol, 80% yield) as a colorless oil which eventually solidified. 1H NMR (400 MHz, CDCl3): δ 7.42-7.32 (m, 5H), 6.69-6.67 (m, 2H), 5.08 (s, 2H), 3.89 (s, 3H), 3.70 (s, 2H).

Workup

  1. temperaturebefore cooling to rt
  2. extractionthe resulting aqueous mixture was extracted with ethyl acetate
  3. washThe organic phase was washed twice with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (80% hexanes, 20% ethyl acetate)

Sources & evidence

ORD record
ord-35250df03f734a47bfdc955776ebcdc0
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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