4-Fluorobenzonitrile → 2-[2-(4-Cyano-phenoxy)-1-hydroxy-1-methyl-ethyl]-6-trifluoromethyl-1H-indole-5-carbonitrile

HRID 1616206Notes

Reaction equation

HRID 1616206 reaction equation
[OH:1][C:2]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]#[N:16])=[C:10]([C:17]([F:20])([F:19])[F:18])[CH:9]=2)([CH3:5])[CH2:3][OH:4].[H-].[Na+].F[C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=1>CN(C=O)C>[C:28]([C:27]1[CH:30]=[CH:31][C:24]([O:4][CH2:3][C:2]([C:6]2[NH:7][C:8]3[C:13]([CH:14]=2)=[CH:12][C:11]([C:15]#[N:16])=[C:10]([C:17]([F:20])([F:18])[F:19])[CH:9]=3)([OH:1])[CH3:5])=[CH:25][CH:26]=1)#[N:29]

Participants

5

Reactant 3

HCID 145174-FluorobenzonitrileHCID 24758Sodium hydrideHCID 668644952-(1,2-Dihydroxy-1-methyl-ethyl)-6-trifluoromethyl-1H-indole-5-carbonitrile

Product 1

HCID 668653412-[2-(4-Cyano-phenoxy)-1-hydroxy-1-methyl-ethyl]-6-trifluoromethyl-1H-indole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(1,2-dihydroxy-1-methyl-ethyl)-6-trifluoromethyl-1-H-indole-5-carbonitrile (209.6 mg, 0.7374 mmol) in dry DMF (4 ml) was added NaH (60 mg, 1.4749 mmol, 60% in mineral oil). After the reaction mixture was stirred at room temperature for 30 min., 4-fluorobenzonitrile (98.15 mg, 0.8115 mmol) was added, and the reaction mixture stirred at room temperature. After HPLC indicated the consumption of starting material, the reaction mixture was poured onto water and extracted with ethyl acetate. The organic layer was washed with 10% LiCl, brine and dried over MgSO4. Column chromatography (EtOAc/Hexanes 50%-100%) yielded the title product as a light yellow powder.

Workup

  1. stirringthe reaction mixture stirred at room temperature
  2. customthe consumption of starting material
  3. additionthe reaction mixture was poured onto water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with 10% LiCl, brine
  6. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-54580a295fa44e5e921d4da461300b82
Source dataset
uspto-grants-2014_07
Patent number
US08765782B2

Reaction notes

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