Benzyl Alcohol → 2-(Benzyloxy)-5-fluorobenzonitrile

HRID 1666752Notes

Reaction equation

HRID 1666752 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.F[C:12]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:13]=1[C:14]#[N:15]>CN(C=O)C>[CH2:3]([O:10][C:12]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:13]=1[C:14]#[N:15])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 1235582,5-Difluorobenzonitrile

Product 1

HCID 582814722-(Benzyloxy)-5-fluorobenzonitrileYield 99.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

In a 12 L, 4-neck round bottom flask equipped with a mechanic stirrer and temperature probe, a suspension of sodium hydride (74 g, 1.82 mol) in DMF (1.95 L) was added benzyl alcohol (142 g, 1.3 mol) through a dropping funnel slowly over 30 minutes in an ice bath under nitrogen. The mixture was stirred in an ice bath (0° C.) for 120 minutes, a solution of 2,5-difluorobenzonitrile (180 g, 1.3 mol) in DMF (650 mL) was added through a dropping funnel over 35 minutes. The resulting mixture was warmed up to room temperature. After 2 hours, the mixture was cooled in an ice bath (4° C.) and quenched with saturated NH4Cl (130 mL) followed by the addition of water (2.6 L×3). The slurry was stirred at room temperature overnight and the precipitate was filtered and washed with water (650 mL×3). The solid was dried in vacuum for 2 days to give 292 g (99.3%) of the desired compound. 1H NMR (400 MHz, DMSO-d6) δ 7.78 (dd, 1H, J=3.2 Hz, J=8.2 Hz), 7.5-7.76 (m, 1H), 7.35-7.48 (m, 6H), 5.28 (s, 2H).

Workup

  1. customIn a 12 L, 4-neck round bottom flask equipped with a mechanic stirrer
  2. temperatureThe resulting mixture was warmed up to room temperature
  3. waitAfter 2 hours
  4. temperaturethe mixture was cooled in an ice bath (4° C.)
  5. customquenched with saturated NH4Cl (130 mL)
  6. additionfollowed by the addition of water (2.6 L×3)
  7. stirringThe slurry was stirred at room temperature overnight
  8. filtrationthe precipitate was filtered
  9. washwashed with water (650 mL×3)
  10. customThe solid was dried in vacuum for 2 days

Sources & evidence

ORD record
ord-3ef0b7243d10487eb314a2041e1094de
Source dataset
uspto-grants-2011_10
Patent number
US08044083B2

Reaction notes

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