Potassium Iodide → 4-(Benzyloxy)-2-fluorobenzonitrile

HRID 1498551Notes

Reaction equation

HRID 1498551 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.[I-].[K+]>CC(C)=O.O>[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

7

Reactant 4

HCID 4875Potassium IodideHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 27346752-Fluoro-4-hydroxybenzonitrile

Product 1

HCID 113336284-(Benzyloxy)-2-fluorobenzonitrileYield 90%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

A solution of 2-fluoro-4-hydroxy-benzonitrile (80 g, 0.58 mol), potassium carbonate (162 g, 1.17 mol) and benzyl bromide (76.4 mL, 0.64 mol) and potassium iodide (9.6 g, 0.058 mol) in acetone (600 mL) was stirred at RT and a significant exothermic reaction was observed. Stirring continued for 18 h without cooling. Reaction progress was monitored by TLC analysis. The reaction mixture was diluted with H2O (600 mL) and extracted with EtOAc (500 mL×2). The combined organic extracts were washed with saturated aqueous NaCl solution (500 mL), dried over Na2SO4, filtered and concentrated in vacuo. The resultant residue was triturated in cyclohexane (300 mL) and the crystalline solid was filtered off and washed to afford 4-Benzyloxy-2-fluoro-benzonitrile (118.2 g, 90%). 1H NMR (400 MHz, CDCl3): 7.51 (1 H, dd, J=8.70, 7.48 Hz), 7.40 (5 H, m), 6.86-6.76 (2 H, m), 5.11 (2 H, s).

Workup

  1. customa significant exothermic reaction
  2. temperaturewithout cooling
  3. customReaction progress
  4. extractionextracted with EtOAc (500 mL×2)
  5. washThe combined organic extracts were washed with saturated aqueous NaCl solution (500 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resultant residue was triturated in cyclohexane (300 mL)
  10. filtrationthe crystalline solid was filtered off
  11. washwashed

Sources & evidence

ORD record
ord-bbfaddcdd70745339004cc5bdcb88bb5
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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