2,6-Dimethoxyphenol → 4-Bromo-2,6-dimethoxyphenol

HRID 1723913Notes

Reaction equation

HRID 1723913 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[OH:11].[Br:12]N1C(=O)CCC1=O>[H-].[Na+].C(Cl)(Cl)Cl>[Br:12][C:7]1[CH:6]=[C:5]([O:9][CH3:10])[C:4]([OH:11])=[C:3]([O:2][CH3:1])[CH:8]=1

Participants

5

Reactant 2

HCID 70412,6-DimethoxyphenolHCID 67184N-bromobutanimide

Product 1

HCID 148458764-Bromo-2,6-dimethoxyphenolYield 22%

Reagents, catalysts & solvents 2

HCID 24758Sodium hydrideCatalystHCID 6212ChloroformSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a 500 mL flask fitted with a condenser, 2,6-dimethoxyphenol (10 g, 64.86 mmol) and 80 mL of anhydrous CHCl3 was added. The solution was cooled to −40° C. and NaH (60% dispersion in mineral oil, 26 mg, 0.65 mmol) was added. Another 20 mL of anhydrous CHCl3 was added followed by rapid addition of N-bromo-succinimide (12.77 g, 71.35 mmol). The reaction mixture was stirred for 1 hour at −35° C., heated to room temperature over the next 30 minutes and heated to reflux for another 30 minutes. The solvent was evaporated under vacuum overnight. The tan solid was stirred with 100 mL ether, the mixture was filtered, and the residue was washed with ether. The solvent was evaporated under vacuum to yield a tan solid, which was then dissolved in boiling hexanes. The solution was decanted from the brown oil and filtered through a pre-heated celite pad into a heated flask. The light yellow solution was allowed to cool at room temperature for 3 hours. White wooly needles were filtered off and dried to yield 217 (3.22 g, 22 %). 1H NMR (CDCl3) δ 6.72 (s, 2H), 5.44 (s, 1H), 3.88 (s, 6H); 13C NMR (CDCl3) 147.47, 133.93, 110.88, 108.38, 56.33.

Workup

  1. customTo a 500 mL flask fitted with a condenser
  2. temperatureheated to room temperature over the next 30 minutes
  3. temperatureheated
  4. temperatureto reflux for another 30 minutes
  5. customThe solvent was evaporated under vacuum overnight
  6. stirringThe tan solid was stirred with 100 mL ether
  7. filtrationthe mixture was filtered
  8. washthe residue was washed with ether
  9. customThe solvent was evaporated under vacuum
  10. customto yield a tan solid, which
  11. dissolutionwas then dissolved
  12. customThe solution was decanted from the brown oil
  13. filtrationfiltered through a pre-heated celite pad into a heated flask
  14. temperatureto cool at room temperature for 3 hours
  15. filtrationWhite wooly needles were filtered off
  16. customdried

Sources & evidence

ORD record
ord-4ec4dafc63dd44d396c06553feb0336d
Source dataset
uspto-grants-2009_02
Patent number
US07485660B2

Reaction notes

Loading…