Phenol → 2-phenoxy-6-(1-piperidinyl)Benzonitrile

HRID 1499114Notes

Reaction equation

HRID 1499114 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].F[C:11]1[CH:18]=[CH:17][CH:16]=[C:15]([N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:12]=1[C:13]#[N:14]>CN(C=O)C.O>[O:7]([C:11]1[CH:18]=[CH:17][CH:16]=[C:15]([N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:12]=1[C:13]#[N:14])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 27800612-Fluoro-6-(piperidin-1-yl)benzonitrile

Product 1

HCID 1179420612-phenoxy-6-(1-piperidinyl)Benzonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of phenol (415 mg, 4.5 mmol) in 60 mL of DMF was added NaH (60%, 6.0 mmol) at 0° C. The reaction was stirred for 1 h, then 2-fluoro-6-(piperidin-1-yl)benzonitrile (CAS#646989-68-6) (612 mg, 3.0 mmol) was added and the reaction stirred for 48 h at RT. The reaction mixture was then diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, then concentrated in vacuo. Purification by normal phase silica gel column chromatography (EtOAc/heptane) provided 2-phenoxy-6-(piperidin-1-yl)benzonitrile as an off-white solid.

Workup

  1. stirringthe reaction stirred for 48 h at RT
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customPurification by normal phase silica gel column chromatography (EtOAc/heptane)

Sources & evidence

ORD record
ord-e90b0649b7d84a0b9a8c51b110c50bbd
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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