3-Methoxyphenol → 2-Bromo-5-methoxyphenol

HRID 1167310Notes

Reaction equation

HRID 1167310 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1.[Br:10]N1C(=O)CCC1=O.C(=O)(O)[O-].[Na+]>O1CCCC1>[Br:10][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=1[OH:9].[Br:10][C:8]1[C:3]([O:2][CH3:1])=[CH:4][C:5]([OH:9])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 90073-MethoxyphenolHCID 67184N-bromobutanimideHCID 516892Sodium Bicarbonate

Product 2

HCID 3479554-Bromo-3-methoxyphenolYield 24%HCID 134938392-Bromo-5-methoxyphenolYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-methoxy-phenol (1 g, 8.055 mmol) in tetrahydrofuran (30 mL) at room temperature was added N-bromosuccinimide (1.478 g, 8.055 mmol) in several portions. The yellow reaction mixture was stirred at room temperature for 12 h. Sodium bicarbonate solution (5 mL) was added and the product was extracted with diethyl ether (2×100 mL). The organic layers were washed with brine (1×20 mL) and dried over anhydrous sodium 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 10-30% ethyl acetate in hexanes yielded 2-bromo-5-methoxy-phenol (0.801 g, 49%) and 4-bromo-5-methoxy-phenol (0.396 g, 24%).

Workup

  1. extractionthe product was extracted with diethyl ether (2×100 mL)
  2. washThe organic layers were washed with brine (1×20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe solid was then filtered off
  5. concentrationthe filtrate was concentrated in vacuo
  6. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
  7. washeluting with 10-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-4caaced538c9496fbb038dd6205cb66e
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

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