Water → HCID 67301852, compound

HRID 1015380Notes

Reaction equation

HRID 1015380 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:19]=[CH:18][CH:17]=[CH:16][C:6]=1[CH2:7][CH:8]1[CH2:13][CH2:12][CH:11]([CH2:14][OH:15])[CH2:10][CH2:9]1.[F:20][C:21]1[CH:28]=[CH:27][CH:26]=[C:25](F)[C:22]=1[C:23]#[N:24].O>CN(C=O)C>[F:20][C:21]1[CH:28]=[CH:27][CH:26]=[C:25]([O:15][CH2:14][CH:11]2[CH2:10][CH2:9][CH:8]([CH2:7][C:6]3[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=3[O:4][CH3:3])[CH2:13][CH2:12]2)[C:22]=1[C:23]#[N:24]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 746952,6-DifluorobenzonitrileHCID 67301798HCID 67301798, compound

Product 1

HCID 67301852HCID 67301852, compoundYield 28.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a cold (ice water) suspension of sodium hydride (0.043 g; 1.1 mmol) in anhydrous DMF (1.4 mL) is added a solution of [4-(2-methoxybenzyl)cyclohexyl]methanol (0.21 g, 0.9 mmol) in anhydrous DMF (1.4 mL) over 11 minutes. After allowing to room temperature over 2 hours, this solution is added to a cold (ice water) stirred solution of 2,6-difluorobenzonitrile (0.14 g; 0.99 mmol) in anhydrous DMF (1.4 mL), and allowed to room temperature over 18 hours. The mixture was poured into a water (40 mL) solution and extracted with ethyl acetate (EtOAc) (4×10 mL). The combined organic layers were washed with brine (40 mL) and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo to purify by of silica gel flash chromatography, using EtOAc/hexane (gradient system), to obtain 2-fluoro-6-[4-(2-methoxybenzyl)cyclohexylmethoxy]benzonitrile (0.09 g, 28% yield).

Workup

  1. waitallowed to room temperature over 18 hours
  2. extractionextracted with ethyl acetate (EtOAc) (4×10 mL)
  3. washThe combined organic layers were washed with brine (40 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationThe organic layer was concentrated in vacuo
  6. customto purify by of silica gel flash chromatography

Sources & evidence

ORD record
ord-903e2536e8284504957ed93f1120a5ef
Source dataset
uspto-grants-2011_07
Patent number
US07985755B2

Reaction notes

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