Methyl iodide → Benzonitrile, 3-methoxy-5-(methoxymethyl)-

HRID 1167335Notes

Reaction equation

HRID 1167335 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:11][CH3:12])[CH:10]=1)[C:6]#[N:7].[H-].[Na+].[CH3:15]I>O1CCCC1>[CH3:12][O:11][C:9]1[CH:8]=[C:5]([CH:4]=[C:3]([CH2:2][O:1][CH3:15])[CH:10]=1)[C:6]#[N:7]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 229962263-(Hydroxymethyl)-5-methoxybenzonitrile

Product 1

HCID 22996211Benzonitrile, 3-methoxy-5-(methoxymethyl)-Yield 75.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-hydroxymethyl-5-methoxy-benzonitrile (261.1 mg, 1.6 mmol, example 33) in tetrahydrofuran (5 mL) cooled to 0° C. was added sodium hydride (43 mg, 1.68 mmol). The ice-bath was removed and the reaction mixture was stirred at room temperature for 15 min before methyl iodide (149 μL, 2.4 mmol) was added. The reaction mixture was stirred at room temperature for 3 h before being quenched with several drops of saturated ammonium chloride solution. The solvent was removed and the residue was taken up in diethyl ether. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solid was then filtered off, and the filtrate was concentrated in vacuo. Purification of the residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 12% ethyl acetate in hexanes yielded 3-methoxy-5-methoxymethyl-benzonitrile as a colorless oil (213 mg, 75%).

Workup

  1. customThe ice-bath was removed
  2. additionwas added
  3. custombefore being quenched with several drops of saturated ammonium chloride solution
  4. customThe solvent was removed
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe solid was then filtered off
  8. concentrationthe filtrate was concentrated in vacuo
  9. customPurification of the residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
  10. washeluting with 12% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-ceca98495a694b6284abb932710309b7
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

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