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

HRID 1726604Notes

Reaction equation

HRID 1726604 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>[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

5

Reactant 3

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

Product 1

HCID 210698282-(Benzyloxy)-4-fluorobenzonitrileYield 81%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Benzyl alcohol (13 mL, 125 mmol) was slowly added to a stirred suspension of NaH (95%, 2.86 g, 113 mmol) in toluene (200 mL) at room temperature. After 30 min, 2,4-difluorobenzonitrile (15.3 g, 1100 mmol; Aldrich) was added all at once and stirring continued overnight (18 h). After this, the reaction mixture was washed with water (2×25 mL) and brine (25 ml). The organic layer was dried (Na2SO4), filtered and concentrated to give a white slurry which was triturated with hexanes and filtered to afford the title compound as a white solid (20.34 g, 81% yield). 1H NMR (500 MHz, CDCl3): 7.59-7.55 (1H, m), 7.45-7.34 (5H, m), 6.75-6.71 (2H, m), 5.19 (2H, s); 13C NMR (125.76 MHz, DMSO-d6) δ ppm: 71.16, 98.75, 101.54, 101.75, 108.66, 108.84, 115.83, 127.16, 128.58, 128.94, 135.03, 135.44, 135.54, 162.22, 162.31, 165.26, 167.29. LCMS calcd for C14H11FNO: 228.2; found: 228.0.

Workup

  1. washAfter this, the reaction mixture was washed with water (2×25 mL) and brine (25 ml)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a white slurry which
  6. customwas triturated with hexanes
  7. filtrationfiltered

Sources & evidence

ORD record
ord-139e529040934af2812dba9dce670db4
Source dataset
uspto-grants-2009_02
Patent number
US07491819B1

Reaction notes

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