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

HRID 505699Notes

Reaction equation

HRID 505699 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].F[C:12]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:13]=1[C:14]#[N:15]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([O:8][C:12]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:13]=1[C:14]#[N:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 775452,4-Difluorobenzonitrile

Product 1

HCID 210698282-(Benzyloxy)-4-fluorobenzonitrileYield 88%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Benzyl alcohol (3.25 g, 30 mmol) was slowly added to a stirred suspension of sodium hydride (1.15 g, 28.7 mmol) in toluene (50 mL) at room temperature. The mixture was stirred for 30 minutes and then 2,4-difluorobenzonitrile was added all at once and stirring continued overnight. The mixture was quenched with water, extracted three times with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered and condensed. The crude product was dissolved in hot ethyl acetate and triturated with hexanes to give 2-(benzyloxy)-4-fluorobenzonitrile (5.4 g, 23.8 mmol, 88% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 5.30 (s, 2H), 6.99 (td, J=8.46, 2.42 Hz, 1H), 7.29-7.51 (m, 6H), 7.86 (dd, J=8.59, 6.44 Hz, 1H).

Workup

  1. stirringstirring continued overnight
  2. customThe mixture was quenched with water
  3. extractionextracted three times with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customcondensed
  8. customtriturated with hexanes

Sources & evidence

ORD record
ord-3e8cf1d2f9574c78878b3a2b524e71c7
Source dataset
uspto-grants-2010_08
Patent number
US07781428B2

Reaction notes

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