2-Bromophenol → 1-Bromo-2-(methoxymethoxy)benzene

HRID 893732Notes

Reaction equation

HRID 893732 reaction equation
[H-].[Na+].CCCCCC.[Br:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[OH:16].[CH3:17][O:18][CH2:19]Br>CN(C)C=O>[Br:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[O:16][CH2:17][O:18][CH3:19]

Participants

6

Reactant 4

HCID 72442-BromophenolHCID 8058HexaneHCID 24758Sodium hydrideHCID 83093Bromomethyl methyl ether

Product 1

HCID 113104791-Bromo-2-(methoxymethoxy)benzeneYield 97.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The oil was removed from 4.5 g (60% in oil, 112 mmol, Aldrich) of sodium hydride dispersion by three 20-mL washes with hexane then the residue was covered with 75 mL of dimethylformamide (Burdick and Jackson). The resulting mixture was heated to about 50° and 18.1 g (105 mmol, Aldrich) of 2-bromophenol was added dropwise over 15 minutes. Vigorous gas evolution was observed. The reaction was stirred for an additional 30 minutes, and the resulting gray-brown solution was cooled to 0°. Bromomethyl methyl ether (9.6 mL, 117 mmol, Aldrich) was added dropwise over 15 minutes. The reaction mixture was stirred for 1 hour at 0°, then at room temperature for 16 hours. The resulting slurry was partitioned between 200 mL of 1 M aqueous sodium hydroxide solution and 150 mL of 4:1 hexane/diethyl ether. The aqueous layer was separated and extracted with an additional 100 mL of 4:1 hexane/diethyl ether. The organic extracts were combined, washed with two 200-mL portions of water, dried (magnesium sulfate) and concentrated in vacuo to give 22.2 g (102 mmol, 97%) of title compound as a pale yellow liquid.

Workup

  1. temperatureThe resulting mixture was heated to about 50°
  2. temperaturethe resulting gray-brown solution was cooled to 0°
  3. stirringThe reaction mixture was stirred for 1 hour at 0°
  4. waitat room temperature for 16 hours
  5. customThe resulting slurry was partitioned between 200 mL of 1 M aqueous sodium hydroxide solution and 150 mL of 4:1 hexane/diethyl ether
  6. customThe aqueous layer was separated
  7. extractionextracted with an additional 100 mL of 4:1 hexane/diethyl ether
  8. washwashed with two 200-mL portions of water
  9. dry with materialdried (magnesium sulfate)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-78e1e67f708e40678910f155f2a8625a
Source dataset
uspto-grants-1992_06
Patent number
US05126370

Reaction notes

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