Methyl iodide → 5-Bromo-1,3-dichloro-2-methoxybenzene

HRID 227361Notes

Reaction equation

HRID 227361 reaction equation
CI.[C:3]([O-:6])([O-])=O.[K+].[K+].[Br:9][C:10]1[CH:15]=[C:14]([Cl:16])[C:13](O)=[C:12]([Cl:18])[CH:11]=1.C(OCC)(=O)C>CN(C=O)C>[Br:9][C:10]1[CH:15]=[C:14]([Cl:16])[C:13]([O:6][CH3:3])=[C:12]([Cl:18])[CH:11]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 185874-Bromo-2,6-dichlorophenol

Product 1

HCID 129634165-Bromo-1,3-dichloro-2-methoxybenzeneYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methyl iodide (467 TL, 8.12 mmol) and K2CO3 (2.24 g, 16.24 mmol) were added to a solution of 4-bromo-2,6-dichlorophenol (982 mg, 4.06 mmol) in DMF (10 mL) and stirred at rt under Ar for 40 min. Upon completion, ethyl acetate was added and the reaction was washed with 1% HCl (2×20 mL), brine (1×), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (hexane) to afford 4-bromo-2,6-dichloroanisole (768 mg, 74%) as a white solid. See, for example, Li, J.; et al. J. Med. Chem. 1996, 39, 1846-1856, which is incorporated by reference in its entirety. 1H NMR (DMSO-d6, 400 MHz) δ 7.75 (s, 2H), 3.81 (s, 3H). 13C NMR (DMSO-d6, 100 MHz) δ 151.3, 131.5, 129.6, 116.5, 60.6. HREIMS calculated for C7H5BrCl2O (M+) 253.8905. found 253.8901.

Workup

  1. washthe reaction was washed with 1% HCl (2×20 mL), brine (1×)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography (hexane)

Sources & evidence

ORD record
ord-71a8e33f3cf743b99d27fd46f13ac848
Source dataset
uspto-grants-2009_07
Patent number
US07560488B2

Reaction notes

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