Chloromethyl Methyl Ether → 1,3-Dibromo-5-(methoxymethoxy)benzene

HRID 1677526Notes

Reaction equation

HRID 1677526 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([OH:11])[CH:7]=[C:8]([Br:10])[CH:9]=1.[CH3:12][O:13][CH2:14]Cl>CN(C=O)C>[Br:3][C:4]1[CH:5]=[C:6]([O:11][CH2:12][O:13][CH3:14])[CH:7]=[C:8]([Br:10])[CH:9]=1

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 122803,5-DibromophenolHCID 24758Sodium hydride

Product 1

HCID 192615801,3-Dibromo-5-(methoxymethoxy)benzeneYield 97.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A flask was charged with sodium hydride (953 mg, 23.8 mmol, 60% in oil), in dry DMF (30 ml) and cooled to 0° C. (ice bath) under nitrogen atmosphere. 3,5-Dibromophenol (5 g, 19.9 mmol) was added in 4 equal portions over 10 minutes. After complete addition the cooling bath was removed and the mixture allowed to warm to ambient temperature over 20 minutes. Chloromethyl methyl ether (1.8 ml, 21.8 mmol) was added slowly, via syringe over about 5 minutes. The mixture was stirred over night. The material was quenched via the addition of saturated aqueous NH4Cl (20 ml) and all volatiles were stripped (rotovap/mechanical pump). The remainder was taken up in water (80 ml) and ethyl acetate (80 ml) and the material shaken in a separtatory funnel. The ethyl acetate phase was collected and washed with an equal volume of brine solution. The aqueous phases were back extracted with ethyl acetate (2×50 ml), the organics combined, dried (MgSO4), filtered and stripped to provide a crude oil. The oil was purified by silica gel chromatography using 4%-6% EtOAc in hexanes as eluant to provide 5.74 g of 1,3-dibromo-5-methoxymethoxy-benzene as a light yellow oil.

Workup

  1. additionAfter complete addition the cooling bath
  2. customwas removed
  3. temperatureto warm to ambient temperature over 20 minutes
  4. customThe material was quenched via the addition of saturated aqueous NH4Cl (20 ml)
  5. stirringethyl acetate (80 ml) and the material shaken in a separtatory funnel
  6. customThe ethyl acetate phase was collected
  7. washwashed with an equal volume of brine solution
  8. extractionThe aqueous phases were back extracted with ethyl acetate (2×50 ml)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customto provide a crude oil
  12. customThe oil was purified by silica gel chromatography

Sources & evidence

ORD record
ord-3663158bb8584423815a92cd82379524
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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