Methyl iodide → 1-Benzyloxy-4-bromo-2,5-dimethoxybenzene

HRID 444625Notes

Reaction equation

HRID 444625 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([O:17][CH3:18])=[CH:11][C:12]([Br:16])=[C:13]([OH:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:21]I>O>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH3:21])[C:12]([Br:16])=[CH:11][C:10]=1[O:17][CH3:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 110881575-(BENZYLOXY)-2-BROMO-4-METHOXYPHENOL

Product 1

HCID 110455271-Benzyloxy-4-bromo-2,5-dimethoxybenzeneYield 88%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

5-Benzyloxy-2-bromo-4-methoxy-phenol 3 (2.76 g, 89.0 mmol) and NaH (0.89 g, 13.0 mmol, 60% dispersion in oil) were added to a flask and flushed with Ar. Dry THF (50 mL) was added and the suspension was stirred in an ice bath for 20 min. CH3I (1.7 mL, 27.0 mmol, filtered through basic alumina) was added and the mixture stirred at room temperature under Ar for 18 h. After cooling the reaction mixture in an ice bath, water was added slowly. The mixture was extracted with ethyl acetate, dried and concentrated to give yellow oil that solidified under vacuum. The oil was purified by silica gel chromatography using silica gel with (10% ethyl acetate/hexanes) to give 2.5 g (88%) of 4 as a white solid. 1H-NMR (400 MHz, CDCl3) dH 3.75 (3H, s, OCH3), 3.84 (3H, s, OCH3), 5.15 (2H, s, CH2Ph), 6.57 (1H, s, ArH), 7.07(1H,s,ArH), 7.32-7.42(5H,m,CH2Ph).

Workup

  1. customflushed with Ar
  2. additionDry THF (50 mL) was added
  3. stirringthe mixture stirred at room temperature under Ar for 18 h
  4. temperatureAfter cooling the reaction mixture in an ice bath
  5. extractionThe mixture was extracted with ethyl acetate
  6. customdried
  7. concentrationconcentrated
  8. customto give yellow oil that
  9. customThe oil was purified by silica gel chromatography

Sources & evidence

ORD record
ord-73c156f752004dc4821fbba732040bf2
Source dataset
uspto-grants-2013_07
Patent number
US08475776B2

Reaction notes

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