Benzyl Bromide → 4-(Benzyloxy)-2-fluorobenzonitrile

HRID 1486795Notes

Reaction equation

HRID 1486795 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(=O)([O-])[O-].[K+].[K+].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C=O)C>[CH2:17]([O:10][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 27346752-Fluoro-4-hydroxybenzonitrile

Product 1

HCID 113336284-(Benzyloxy)-2-fluorobenzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

To a stirred solution of 2-fluoro-4-hydroxybenzonitrile, 29 (15.00 g, 0.1094 mol) in DMF (45.0 mL) cooled to 0° C. was added potassium carbonate (37.8 g, 0.274 mol) followed by stifling at 0-5° C. for 30 min. Benzyl bromide (13.7 mL, 0.115 mol) was added to the reaction mixture at <5° C., stirred at 5° C. for 1 h followed by warming to 20° C. and stirring for additional 2.5 h. The completed reaction was partitioned between water (180 ml) and MTBE (220 mL), the layers separated and the organic layer was washed with water (90 mL), concentrated and azeotroped to dry two times with EtOAc (150 mL each) to provide 4-(benzyloxy)-2-fluorobenzonitrile, 30 (24.64 g, 0.1084 mol, 99% yield) as white solid.

Workup

  1. temperatureby warming to 20° C.
  2. stirringstirring for additional 2.5 h
  3. customThe completed reaction
  4. customwas partitioned between water (180 ml) and MTBE (220 mL)
  5. customthe layers separated
  6. washthe organic layer was washed with water (90 mL)
  7. concentrationconcentrated
  8. customazeotroped
  9. dry with materialto dry two times with EtOAc (150 mL each)

Sources & evidence

ORD record
ord-96d4fb36afc247319a344594a376f285
Source dataset
uspto-grants-2016_08
Patent number
US09428495B2

Reaction notes

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