Methyl iodide → 6-Bromo-2,2-dimethyl-1,1-dioxido-2,3-dihydro-1-benzothien-3-yl methyl ether

HRID 2390298Notes

Reaction equation

HRID 2390298 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:17]=[CH:16][C:7]2[CH:8]([OH:15])[C:9]([CH3:14])([CH3:13])[S:10](=[O:12])(=[O:11])[C:6]=2[CH:5]=1.I[CH3:19]>CN(C=O)C>[CH3:19][O:15][CH:8]1[C:7]2[CH:16]=[CH:17][C:4]([Br:3])=[CH:5][C:6]=2[S:10](=[O:11])(=[O:12])[C:9]1([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 565941116-Bromo-2,2-dimethyl-2,3-dihydro-1-benzothiophene-3-ol 1,1-dioxide2×

Product 1

HCID 565941136-Bromo-2,2-dimethyl-1,1-dioxido-2,3-dihydro-1-benzothien-3-yl methyl ether

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A cooled (0° C.) suspension of NaH (20.61 mg; 0.52 mmol; 1.00 eq.) in dry DMF was carefully treated with solution of 6-bromo-2,2-dimethyl-2,3-dihydro-1-benzothiophene-3-ol 1,1-dioxide (Intermediate 244; 150 mg; 0.52 mmol) in anhydrous DMF. The reaction mixture was stirred at RT for 4 min then treated with a 3 M solution of iodomethane (240 μl; 0.72 mmol). The mixture was stirred at RT for 2.5 h, then quenched with water. EtOAc was added, the phases were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried over anhydrous magnesium sulfate and concentrated to dryness to afford a residue, which was purified by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc. The title compound was obtained as a white solid.

Workup

  1. temperatureA cooled
  2. stirringThe mixture was stirred at RT for 2.5 h
  3. customquenched with water
  4. additionEtOAc was added
  5. customthe phases were separated
  6. extractionthe aqueous phase was extracted with EtOAc
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated to dryness
  10. customto afford a residue, which
  11. customwas purified by flash column chromatography (silica)
  12. washeluting with cyclohexane containing
  13. temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record
ord-67a7d4a9cf5b4d339c88be8cb37a4249
Source dataset
uspto-grants-2012_09
Patent number
US08273769B2

Reaction notes

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