Methyl iodide → 4-(Benzyloxy)-2-methoxybenzonitrile

HRID 1784478Notes

Reaction equation

HRID 1784478 reaction equation
[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([OH:17])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I[CH3:19].[H-].[Na+]>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([O:17][CH3:19])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 154532344-(Benzyloxy)-2-hydroxybenzonitrile

Product 1

HCID 225917204-(Benzyloxy)-2-methoxybenzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a magnetically stirred solution of 4-benzyloxy-2-hydroxybenzonitrile (1-A, WO 00/69841) (7.95 g, 35.3 mmol) and iodomethane (5.43 mL, 87.2 mmol) in DMF (90 mL) cooled to −5° was added all at once sodium hydride (60% dispersion, 2.17 g, 54.2 mmol). The mixture was stirred for 30 min, warmed to room temperature and stirred for an additional 2 h. Most of the DMF was removed in vacuo, and the residue was partitioned between water and ethyl acetate. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with water and saturated brine and dried (MgSO4). The residue after removal of the solvent in vacuo was triturated with hexane and chromatographed on silica gel with hexanes —CH2Cl2 (2:3) to give 4-benzyloxy-2-methoxybenzonitrile (1-B). MS: m/z 240 (M+1); 1H NMR (500 MHz, CDCl3): δ 7.47 (d, 1H, J=8.4 Hz), 7.36-7.45 (m, 5H), 6.58 (dd, 1H, J=2.3, 8.4 Hz), 6.57 (d, 1H, J=2.3 Hz), 5.10 (s, 2H), 3.88 (s, 3H) ppm.

Workup

  1. stirringstirred for an additional 2 h
  2. customMost of the DMF was removed in vacuo
  3. customthe residue was partitioned between water and ethyl acetate
  4. extractionThe aqueous phase was extracted three times with ethyl acetate
  5. washThe combined organic phases were washed with water and saturated brine
  6. dry with materialdried (MgSO4)
  7. customThe residue after removal of the solvent in vacuo
  8. customwas triturated with hexane
  9. customchromatographed on silica gel with hexanes —CH2Cl2 (2:3)

Sources & evidence

ORD record
ord-5c7803fc28434ac2bf2d75784aa563f6
Source dataset
uspto-grants-2009_03
Patent number
US07504402B2

Reaction notes

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