Reaction #69548

Reaction equation

1-[2,6-dimethoxy-4-(methoxymethyl)phenyl]ethanone

triethylamine

tert-butyldimethylsilyl trifluoromethanesulfonate

ammonium chloride

N-bromosuccinimide

tetrabutylammonium fluoride

sodium hydrogencarbonate

→

title compound

Yield 88.2%

2-Bromo-[2,6-dimethoxy-4-(methoxymethyl)phenyl]ethanone

Yield 88.2%

Solvents

tetrahydrofuran

n-heptane ethyl acetate

tetrahydrofuran

Conditions

Workup

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   Temperaturewhile cooling on ice
3. 3
   workup.STIRRINGthe mixture was stirred for 1.5 hours
4. 4
   Extractionthe reaction mixture was extracted with ethyl acetate
5. 5
   Dryingdried over magnesium sulfate
6. 6
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
7. 7
   Temperaturewhile cooling on ice
8. 8
   workup.STIRRINGthe mixture was stirred for 30 minutes
9. 9
   Extractionthe mixture was extracted with ethyl acetate
10. 10
    Dryingdried over magnesium sulfate
11. 11
    workup.DISTILLATIONthe solvent was distilled off under reduced pressure
12. 12
    OtherThe residue was purified by silica gel column chromatography (a mixed solvent of n-heptane and ethyl acetate

Procedure

To a tetrahydrofuran (120 mL) solution of 1-[2,6-dimethoxy-4-(methoxymethyl)phenyl]ethanone (10.0 g, 44.9 mmol) was added triethylamine (18.8 ml, 135 mmol), and tert-butyldimethylsilyl trifluoromethanesulfonate (15.5 ml, 67.4 mmol) was added dropwise while cooling on ice, and the mixture was stirred for 30 minutes. N-bromosuccinimide (12.0 g, 67.4 mmol) was added and the mixture was stirred for 1.5 hours. To the reaction mixture, a saturated aqueous solution sodium hydrogencarbonate was added, and the reaction mixture was extracted with ethyl acetate, and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. To a tetrahydrofuran (80 mL) solution was added dropwise tetrabutylammonium fluoride (1M, 40.4 ml, 40.4 mmol) while cooling on ice, and the mixture was stirred for 30 minutes. To the mixture was added a saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate and dried over magnesium sulfate, and then the solvent 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 3/1 then 2/1) to obtain the title compound (12.0 g, 39.6 mmol).

Source