Water → 1-Bromo-3-(4-methoxybenzyloxy)-2-methylbenzene

HRID 1820697Notes

Reaction equation

HRID 1820697 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](F)[C:3]=1[CH3:9].[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][OH:19])=[CH:14][CH:13]=1.[H-].[Na+].O>CN(C=O)C.[Cl-].[Na+].O.CCCCCCC.C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:19][CH2:18][C:15]2[CH:16]=[CH:17][C:12]([O:11][CH3:10])=[CH:13][CH:14]=2)[C:3]=1[CH3:9]

Participants

9

Reactant 4

HCID 962WaterHCID 77384-Methoxybenzyl alcoholHCID 24758Sodium hydrideHCID 27363352-Bromo-6-fluorotoluene

Product 1

HCID 668818551-Bromo-3-(4-methoxybenzyloxy)-2-methylbenzeneYield 46%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8900HeptaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

1-Bromo-3-fluoro-2-methylbenzene (388 mg, 2.05 mmol), and (4-methoxyphenyl)methanol (0.511 mL, 4 mmol) were dissolved in DMF (5 mL) in a microwave vessel. Sodium hydride as a 60% dispersion in mineral oil (164 mg, 4.0 mmol) was added portionwise under a flow of nitrogen over 10 min. The reaction vessel was then sealed and heated at 180° C. for 900s. The crude reaction mixture was poured onto 1:1 water:brine (6 mL) and DCM (10 mL). The biphasic mixture was stirred at ambient temperature for 1 h and then the organic and aqueous layers were separated. The combined organics were dried over Na2SO4 and concentrated in vacuo. The crude material was then purified by chromatography on silica gel. Elution with 5:95 ethyl acetate:heptane afforded 1-bromo-3-(4-methoxybenzyloxy)-2-methylbenzene (289 mg, 0.9 mmol, 46%).

Workup

  1. customThe reaction vessel was then sealed
  2. customThe crude reaction mixture
  3. customthe organic and aqueous layers were separated
  4. dry with materialThe combined organics were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was then purified by chromatography on silica gel
  7. washElution with 5:95 ethyl acetate

Sources & evidence

ORD record
ord-dc8c987f83e246a5a1e324424767899d
Source dataset
uspto-grants-2009_10
Patent number
US07605170B2

Reaction notes

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