Dimethyl Sulfate → 2-Methoxy-4-methylbenzonitrile

HRID 1157861Notes

Reaction equation

HRID 1157861 reaction equation
[OH:1][C:2]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].O.[OH-].[Li+].S(OC)(O[CH3:18])(=O)=O>C1COCC1.C(OCC)C>[CH3:18][O:1][C:2]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

6

Reactant 3

HCID 6497Dimethyl SulfateHCID 168937Lithium hydroxide, monohydrateHCID 143886562-Hydroxy-4-methylbenzonitrile

Product 1

HCID 124953732-Methoxy-4-methylbenzonitrileYield 90%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-Hydroxy-4-methylbenzonitrile (0.46 g, 3.46 mmol) in THF (17 mL) was added lithium hydroxide monohydrate (0.292 g, 6.95 mmol) followed by dimethyl sulfate (0.50 mL, 5.28 mmol). The resultant mixture was heated to reflux for 2 hours then cooled to room temperature. The mixture was diluted with diethyl ether (50 mL), washed with saturated aqueous NaHCO3 (3×15 mL), dried (MgSO4) and concentrated. Purification of the crude material by column chromatography on silica gel (4:1 hexanes-EtOAc) provided 0.456 g (90%) of 2-methoxy-4-methylbenzonitrile as a white solid. 1H NMR (CDCl3) δ 2.41 (s, 3H), 3.91 (s, 3H), 6.77 (s, 1H), 6.81 (d, 1H, J=6 Hz), 7.43 (d, 1H, J=6 Hz). ES-MS m/z 148 (M+H).

Workup

  1. temperatureto reflux for 2 hours
  2. washwashed with saturated aqueous NaHCO3 (3×15 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customPurification of the crude material by column chromatography on silica gel (4:1 hexanes-EtOAc)

Sources & evidence

ORD record
ord-74005f83e0e34a329440f93292332fac
Source dataset
uspto-grants-2010_10
Patent number
US07807694B2

Reaction notes

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