Sodium hydride → 2-(5-Chloro-2-methoxybenzyloxy)-6-fluorobenzonitrile

HRID 2177004Notes

Reaction equation

HRID 2177004 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([O:12][CH3:13])=[C:8]([CH:11]=1)[CH2:9][OH:10].[F:14][C:15]1[CH:22]=[CH:21][CH:20]=[C:19](F)[C:16]=1[C:17]#[N:18]>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([O:12][CH3:13])=[C:8]([CH:11]=1)[CH2:9][O:10][C:19]1[CH:20]=[CH:21][CH:22]=[C:15]([F:14])[C:16]=1[C:17]#[N:18]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 746952,6-DifluorobenzonitrileHCID 4357585(5-Chloro-2-methoxyphenyl)methanol

Product 1

HCID 669243522-(5-Chloro-2-methoxybenzyloxy)-6-fluorobenzonitrileYield 80.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a cold (ice water) suspension of sodium hydride (472 mg; 11.8 mmol) in anhydrous DMF (5 mL) is added a solution of 5-chloro-2-methoxybenzyl alcohol (1.72 g; 9.7 mmol) in anhydrous DMF (5 mL) over 15 minutes. After allowing to room temperature over 1 hour, this solution is added to a cold (ice water) stirred solution of 2,6-difluorobenzonitrile (1.63 g; 11.3 mmol) in anhydrous DMF (8 mL), and allowed to room temperature over 3 hours. The reaction mixture is poured into ice water with vigorous stirring and the resulting solid is filtered, washed with water, and dried under vacuum at 45° C. overnight to give 2.28 grams of 2-(5-chloro-2-methoxybenzyloxy)-6-fluorobenzonitrile.

Workup

  1. waitallowed to room temperature over 3 hours
  2. filtrationthe resulting solid is filtered
  3. washwashed with water
  4. customdried under vacuum at 45° C. overnight

Sources & evidence

ORD record
ord-43583944a2334eef9ff5b7c84d4c5343
Source dataset
uspto-grants-2015_06
Patent number
US09067897B2

Reaction notes

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