1,2-Dimethoxyethane → 4-Benzyloxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one

Participants

Reaction Conditions

Reaction Steps

To 4-benzyloxy-5-bromo-1-methyl-1,3-dihydro-indol-2-one (100 mg, 0.301 mmol) was added 3-pyridineboronic acid (CAS#1692.25-7, 44.4 mg, 0.361 mmol), 1,2-dimethoxyethane (2 mL) and 2 M aqueous sodium carbonate (0.376 ml, 0.753 mmol). The reaction mixture was degassed and placed under an argon atmosphere, at which time resin bound tetrakis(triphenylphosphine)palladium(0), specifically polystyrene triphenylphosphine palladium (0) [PS—PPh3-Pd(0) (Biotage), 0.11 mmol/g loading, (82 mg, 0.0093 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 130° C. for 2.5 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane and filtered through glass wool. The filtrate was further diluted with saturated aqueous sodium bicarbonate and the layers were separated. The aqueous layer was extracted two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0 to 100%) to afford 4-benzyloxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 331.1447 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.16 (s, 3H), 3.77 (s 2H), 4.93 (s, 2H), 6.88 (d J=8.08 Hz, 1H), 7.16-7.21 (m, 2H), 7.27-7.31 (m, 3H), 7.35 (d, J=8.08 Hz, 1H), 7.41 (qd, 1H), 7.86 (dt, J=7.83, 2.02 Hz, 1H), 5.52 (dd, J=4.80, 1.77 Hz, 1H), 8.67 (dd, J=2.27, 0.76 Hz, 1H).

Provenance & Evidence