Acetonitrile → 1-Bromo-4-methoxy-2-phenylmethoxybenzene

HRID 277501Notes

Reaction equation

HRID 277501 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[OH:10].CC#N.C([O-])([O-])=O.[K+].[K+].[CH2:20](Cl)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[O:10][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 7503Benzyl ChlorideHCID 11430Potassium CarbonateHCID 134938392-Bromo-5-methoxyphenol

Product 1

HCID 184340291-Bromo-4-methoxy-2-phenylmethoxybenzeneYield 102.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 12 L four-necked round-bottomed flask equipped with mechanical stirrer, thermometer and reflux condenser with nitrogen inlet was charged with 2-bromo-5-methoxyphenol (615 g, 2.98 mol), CH3CN (6 L), K2CO3 (671 g, 4.77 mol), benzyl chloride (363 mL, 3.14 mol), and KI (6 g, 0.036 mol). The mixture was heated to reflux for 3 h, cooled to room temperature, and H2O (3 L) added to form a biphasic mixture. The aqueous layer was separated, CH3CN (3 L) removed in vacuo and EtOAc (4 L) added to extract the product. After a wash with H2O (3 L) and 10% NaCl solution (1.8 L), the organic layer was concentrated to dryness to afford 1-bromo-4-methoxy-2-(phenylmethoxy)benzene as a light yellow oil (895.5 g, 99%): 110° C. (2.5 mm Hg); 1H NMR δ7.55-7.25 (m, 6H), 6.55 (d, J=2.7 Hz, 1H), 6.35 (dd, J=8.5 Hz, 1.5 Hz, 1H), 5.1 (s, 2H), 3.75 (s, 3H).

Workup

  1. customA 12 L four-necked round-bottomed flask equipped with mechanical stirrer
  2. temperaturethermometer and reflux condenser with nitrogen inlet
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 3 h
  5. customto form a biphasic mixture
  6. customThe aqueous layer was separated
  7. customCH3CN (3 L) removed in vacuo and EtOAc (4 L)
  8. additionadded
  9. extractionto extract the product
  10. washAfter a wash with H2O (3 L) and 10% NaCl solution (1.8 L)
  11. concentrationthe organic layer was concentrated to dryness

Sources & evidence

ORD record
ord-cfef27617b7d4c26b95029b9004c397d
Source dataset
uspto-grants-2002_03
Patent number
US06355813B1

Reaction notes

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