Methyl iodide → 3,3-Dimethyl-1,3-dihydro-indol-2-one

Participants

Reaction Conditions

Reaction Steps

3,3-dimethylindolin-2-one: To a stirred solution of 22a (3.2 g, 18.29 mmol) in dry THF (100 mL) was added MeI (2.6 mL, 41.75 mmol, 2.3 eq), followed by the addition of 18-crown-6 (0.51 g, 4.57 mmol, 0.25 eq) at −78° C. under nitrogen. Potassium tert-butoxide (5.12 g, 45.73 mmol, 2.5 eq) was added portionwise. The resulting slurry was stirred at −78° C. for 1 h. The mixture was stirred at −78° C. to rt for 3 h. Cooled in an ice bath, sat'd NH4Cl was added. It was extracted with EtOAc, washed with H2O, brine, dried over MgSO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, hexanes/EtOAc) to give pure 1-acetyl-3,3-dimethylindolin-2-one (1.3 g) (LC-MS ESI 204(M+H)) and pure 3,3-dimethylindolin-2-one (1.0 g) (LC-MS ESI 162 (M+H)) respectively. 1-Acetyl-3,3-dimethylindolin-2-one (1.3 g) was heated in 6N HCl at reflux for 1 h. After cooling, it was poured into crushed ice. It was extracted with Et2O, washed with sat'd NaHCO3, H2O, brine, dried over Na2SO4, filtered, and concentrated to dryness to give almost pure 3,3-dimethylindolin-2-one (1.0 g).

Provenance & Evidence