Chloromethyl Methyl Ether → HCID 59540873, compound

HRID 1677541Notes

Reaction equation

HRID 1677541 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.[H-].[Na+].Cl[CH2:13][O:14][CH3:15].[NH4+].[Cl-]>CN(C=O)C.C(OCC)(=O)C.O>[Br:8][C:6]1[CH:7]=[C:2]([NH2:1])[CH:3]=[C:4]([O:9][CH2:13][O:14][CH3:15])[CH:5]=1

Participants

8

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 183882723-Amino-5-bromophenol

Product 1

HCID 59540873HCID 59540873, compoundYield 94.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-amino-5-bromo-phenol (3.0 g, 15.96 mmol) in dry DMF (35 ml) was cooled (ice bath) under nitrogen. Sodium hydride (732 g, 18.36 mmol, 60% in oil) was added in 2 equal portions over 5 minutes. After 10 minutes stirring the material was warmed to ambient. Chloromethylmethyl ether (1.38 ml, 18.4 mmol) was added slowly, via syringe. The material was stirred for 2 hours. The solvent was stripped (rotovap/pump) providing a crude remainder which was treated with a solution of saturated aqueous NH4Cl (25 ml), water (35 ml) and ethyl acetate (60 ml). The material was shaken in a reparatory funnel and the organic phase was collected and washed with an equal volume of brine. The aqueous phases were back extracted with ethyl acetate (2×50 ml) and the organics combined, dried (MgSO4), filtered and stripped to provide a viscous oil. The crude was purified by silica gel chromatography using 4%-30% EtOAc in hexanes as eluant to provide 3.50 g of 3-bromo-5-methoxymethoxy-phenylamine as a light yellow mobile oil.

Workup

  1. temperaturewas warmed to ambient
  2. stirringThe material was stirred for 2 hours
  3. customproviding a crude remainder which
  4. stirringThe material was shaken in a reparatory funnel
  5. customthe organic phase was collected
  6. washwashed with an equal volume of brine
  7. extractionThe aqueous phases were back extracted with ethyl acetate (2×50 ml)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customto provide a viscous oil
  11. customThe crude was purified by silica gel chromatography

Sources & evidence

ORD record
ord-b129a3f3529d44df93e557d6d8519bba
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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