Dimethylformamide → 2-Bromo-5-[(cyclobutyloxy)methyl]-1,3-dimethoxybenzene

HRID 41244Notes

Reaction equation

HRID 41244 reaction equation
[CH:1]1([OH:5])[CH2:4][CH2:3][CH2:2]1.CN(C=O)C.[H-].[Na+].[Br:13][C:14]1[C:19]([O:20][CH3:21])=[CH:18][C:17]([CH2:22]Cl)=[CH:16][C:15]=1[O:24][CH3:25]>CCCCCCC.C(OCC)(=O)C.C(OCC)(=O)C.O>[Br:13][C:14]1[C:19]([O:20][CH3:21])=[CH:18][C:17]([CH2:22][O:5][CH:1]2[CH2:4][CH2:3][CH2:2]2)=[CH:16][C:15]=1[O:24][CH3:25]

Participants

8

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 76218CyclobutanolHCID 249719722-Bromo-5-(chloromethyl)-1,3-dimethoxybenzene

Product 1

HCID 579124482-Bromo-5-[(cyclobutyloxy)methyl]-1,3-dimethoxybenzeneYield 85.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

To a mixture of cyclobutyl alcohol (4.16 g, 57.7 mmol) and DMF (30 mL) was added sodium hydride (60% oil dispersion: 2.31 g, 57.7 mmol) while cooling on ice, and the mixture was stirred at room temperature for one hour. To the mixture was gradually added dropwise a mixture of 2-bromo-5-(chloromethyl)-1,3-dimethoxybenzene (2.47 g, 9.3 mmol) and DMF (30 mL), and the mixture was stirred at room temperature for one hour. Water was added to the mixture while cooling on ice, and then ethyl acetate was added. After thoroughly shaking the mixture, the organic layer was separated, and the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The mixture was filtered, and then the solvent in the filtrate was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (a mixed solvent of n-heptane and ethyl acetate: n-heptane/ethyl acetate=4/1) to obtain the title compound (2.39 g, 7.94 mmol).

Workup

  1. temperaturewhile cooling on ice
  2. additionTo the mixture was gradually added dropwise
  3. stirringthe mixture was stirred at room temperature for one hour
  4. temperaturewhile cooling on ice
  5. stirringAfter thoroughly shaking the mixture
  6. customthe organic layer was separated
  7. washthe organic layer was washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe mixture was filtered
  10. distillationthe solvent in the filtrate was distilled off under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (a mixed solvent of n-heptane and ethyl acetate

Sources & evidence

ORD record
ord-5b659e429b134b459463fc5cd1122af5
Source dataset
uspto-grants-2013_09
Patent number
US08530504B2

Reaction notes

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