Isopropyl iodide → 2-Isopropoxy-4-methoxybenzonitrile

HRID 1167303Notes

Reaction equation

HRID 1167303 reaction equation
[OH:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(=O)([O-])[O-].[K+].[K+].I[CH:19]([CH3:21])[CH3:20]>C(O)C.C(OCC)C.O>[CH:19]([O:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5])([CH3:21])[CH3:20]

Participants

7

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 114236802-Hydroxy-4-methoxybenzonitrile

Product 1

HCID 227210812-Isopropoxy-4-methoxybenzonitrileYield 56%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 2-hydroxy-4-methoxy-benzonitrile (16.4 g, 134.1 mmol) in ethanol were added potassium carbonate (37.07 g, 268.2 mmol) and 2-iodopropane (40.16 mL, 402.3 mmol). The reaction mixture was heated at gentle reflux for 3.5 h. The solvent was removed to afford a brown paste. It was then taken in diethyl ether (300 mL) and water (200 mL). The layers were separated and the aqueous layer was extracted with diethyl ether (3×100 mL). The combined organic extracts were washed with brine and dried over anhydrous magnesium sulfate. The solid was then 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 12% ethyl acetate in hexanes yielded 2-isopropoxy-4-methoxy-benzonitrile as a pale-yellow oil (11.8 g, 56%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat gentle reflux for 3.5 h
  3. customThe solvent was removed
  4. customto afford a brown paste
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with diethyl ether (3×100 mL)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe solid was then filtered off
  10. concentrationthe filtrate was concentrated in vacuo
  11. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
  12. washeluting with 12% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3d12bfd886f549729fb2df667d01fa0d
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

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