Reaction #7085

Reaction equation

ammonium chloride

potassium tert-butoxide

5-bromo-3-hydroxy-3-methyl-1,3-dihydro-indol-2-one

methyl-p-toluenesulfonate

→

5-bromo-3-methoxy-3-methyl-1,3-dihydro-indol-2-one

Yield 53.7%

Solvents

DMF

Conditions

Workup

1. 1
   Temperatureto warm up-to room temperature
2. 2
   Extractionextracted with EtOAc (×2)
3. 3
   Washthe combined organic layers were washed with water, sodium hydroxide (1N, ×2), water (×3)
4. 4
   Dryingdried (MgSO4)
5. 5
   Otherevaporated
6. 6
   OtherThe residue was then purified by column chromatography (SiO2, EtOAc: hexane, gradient elution)

Procedure

5-bromo-3-hydroxy-3-methyl-1,3-dihydro-indol-2-one (1.0 g, 4.1 mmol) was dissolved in dry DMF (15 cm3) cooled to 0° C. and treated with potassium tert-butoxide (1M in THF, 4.5 cm3, 4.5 mmol). After 15 min. methyl-p-toluenesulfonate (0.93 g, 5 mmol) was added and the mixture was allowed to warm up-to room temperature. After 2 h the mixture was poured into saturated ammonium chloride solution and extracted with EtOAc (×2), then the combined organic layers were washed with water, sodium hydroxide (1N, ×2), water (×3), dried (MgSO4) and evaporated. The residue was then purified by column chromatography (SiO2, EtOAc: hexane, gradient elution) to afford 5-bromo-3-methoxy-3-methyl-1,3-dihydro-indol-2-one (0.56 g, 2.2 mmol, 53%): 1H NMR (CDCl3) δ 1.59 (s, 3H), 3.18 (s, 3H), 6.73 (d, 1H, J=8.2 Hz), 7.45 (dd, 1H, J=8.2, 2 Hz), 7.52 (d, 1H, J=2 Hz); MS (EI) m/z 225 (M)+.

Source