Methyl iodide → 2,4-Dimethoxy-5-methoxymethyl-benzonitrile

HRID 1167333Notes

Reaction equation

HRID 1167333 reaction equation
[OH:1][CH2:2][C:3]1[C:4]([O:13][CH3:14])=[CH:5][C:6]([O:11][CH3:12])=[C:7]([CH:10]=1)[C:8]#[N:9].[H-].[Na+].I[CH3:18]>O1CCCC1>[CH3:12][O:11][C:6]1[CH:5]=[C:4]([O:13][CH3:14])[C:3]([CH2:2][O:1][CH3:18])=[CH:10][C:7]=1[C:8]#[N:9]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 229962455-Hydroxymethyl-2,4-dimethoxy-benzonitrile

Product 1

HCID 229961882,4-Dimethoxy-5-methoxymethyl-benzonitrileYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-hydroxymethyl-2,4-dimethoxy-benzonitrile (218 mg, 1.128 mmol) in tetrahydrofuran (10 mL) cooled to 0° C. were sequentially added sodium hydride (34.2 mg, 1.354 mmol) and iodomethane (140 μL, 2.256 mmol). The icebath was removed after 5 min and the reaction mixture was stirred at room temperature under argon for 12 h. Water was added and the product was extracted with methylene chloride (2×15 mL). The organic layers were washed with brine (1×2 mL) and dried over anhydrous sodium sulfate. The solid was filtered off and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 40% ethyl acetate in hexanes yielded 2,4-dimethoxy-5-methoxymethyl-benzonitrile as a white solid (221 mg, 95%).

Workup

  1. customThe icebath was removed after 5 min
  2. additionWater was added
  3. extractionthe product was extracted with methylene chloride (2×15 mL)
  4. washThe organic layers were washed with brine (1×2 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe solid was filtered off
  7. concentrationthe filtrate was concentrated in vacuo
  8. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
  9. washeluting with 40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3c1a480ddc8b4c1aa4f3df9902060f06
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

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