Cyclohexanol → 3-Fluoro-5-cyclohexyloxybenzonitrile

HRID 1641244Notes

Reaction equation

HRID 1641244 reaction equation
[H-].[Na+].[CH:3]1([OH:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.F[C:11]1[CH:12]=[C:13]([CH:16]=[C:17]([F:19])[CH:18]=1)[C:14]#[N:15]>CN(C=O)C.CCOCC>[F:19][C:17]1[CH:16]=[C:13]([CH:12]=[C:11]([O:9][CH:3]2[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]2)[CH:18]=1)[C:14]#[N:15]

Participants

6

Reactant 3

HCID 7966CyclohexanolHCID 24758Sodium hydrideHCID 5872043,5-Difluorobenzonitrile

Product 1

HCID 595531353-Fluoro-5-cyclohexyloxybenzonitrile

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (1.92 g, 48.0 mmol) is slowly added to a stirred solution of cyclohexanol (4.01 g, 40.0 mmol) in DMF (30 ml) at 0-5° C. under nitrogen. After 2.5 hours, 3,5-difluorobenzonitrile (5.56 g, 40.0 mmol) is slowly added over 5 min. The mixture is allowed to warm to room temperature and stirred for an additional 12 hours. The mixture is diluted with ether (150 ml), washed with water, brine (30 ml), dried over Na2SO4 and evaporated. The residue is purified by column chromatography on silica gel eluting with ethyl acetate:hexanes (1:10) to provide 3-fluoro-5-cyclohexyloxybenzonitrile as a yellow oil. MS: 220 (M+1).

Workup

  1. washwashed with water, brine (30 ml)
  2. dry with materialdried over Na2SO4
  3. customevaporated
  4. customThe residue is purified by column chromatography on silica gel eluting with ethyl acetate:hexanes (1:10)

Sources & evidence

ORD record
ord-127b9d1932714549980473a2e54ae3e2
Source dataset
uspto-grants-2012_02
Patent number
US08114873B2

Reaction notes

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