Sodium hydride → 2-[1-(2,6-Difluorophenyl)-ethoxy]-6-fluorobenzonitrile

HRID 2177001Notes

Reaction equation

HRID 2177001 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:5]=1[CH:6]([OH:8])[CH3:7].[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>[F:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:5]=1[CH:6]([O:8][C:19]1[CH:20]=[CH:21][CH:22]=[C:15]([F:14])[C:16]=1[C:17]#[N:18])[CH3:7]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 746952,6-DifluorobenzonitrileHCID 50120752,6-Difluoro-alpha-methylbenzyl alcohol

Product 1

HCID 669243422-[1-(2,6-Difluorophenyl)-ethoxy]-6-fluorobenzonitrileYield 69.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a cold (ice water) suspension of sodium hydride (409 mg; 10 mmol) in anhydrous DMF (4 mL) is added a solution of 2,6-difluoro-alpha-methylbenzyl alcohol (1.63 g; 10 mmol) in anhydrous DMF (5 mL) over 10 minutes. After allowing to room temperature over 1 hour, this solution is added to a cold (ice water) stirred solution of 2,6-difluorobenzonitrile (1.53 g; 11 mmol) in anhydrous DMF (6 mL), and allowed to room temperature over 2.5 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 40° C. overnight to give 1.92 grams of 2-[1-(2,6-difluorophenyl)-ethoxy]-6-fluorobenzonitrile.

Workup

  1. waitallowed to room temperature over 2.5 hours
  2. filtrationthe resulting solid is filtered
  3. washwashed with water
  4. customdried under vacuum at 40° C. overnight

Sources & evidence

ORD record
ord-d9e69f69b8ac41c0b9c6dd4ba3c493a5
Source dataset
uspto-grants-2015_06
Patent number
US09067897B2

Reaction notes

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