Methyl p-toluenesulfonate → 5-Bromo-3-methoxy-3-methyl-1,3-dihydro-indol-2-one

HRID 6989

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2([OH:13])[CH3:12].[CH3:14]C(C)([O-])C.[K+].COS(C1C=CC(C)=CC=1)(=O)=O.[Cl-].[NH4+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2([O:13][CH3:14])[CH3:12]

Participants

Conditions

Temperature: 0 °C

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)+.

Workup

temperatureto warm up-to room temperature
extractionextracted with EtOAc (×2)
washthe combined organic layers were washed with water, sodium hydroxide (1N, ×2), water (×3)
dry with materialdried (MgSO4)
customevaporated
customThe residue was then purified by column chromatography (SiO2, EtOAc: hexane, gradient elution)

Sources & evidence

ORD record: ord-a4bc0c246c5c49f69c45dc9f684b7b07
Source dataset: uspto-grants-2006_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07084168B2

Linked notes

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