Reaction Steps
A suspension of 2-(3-bromo-2-methylphenyl)-5-tert-butylisoindoline-1,3-dione (Intermediate 3-2, 1.0 g, 2.69 mmol) in methanol (20 mL) was treated with sodium borohydride (203 mg, 5.37 mmol) and stirred at rt. After a few minutes, additional sodium borohydride (203 mg, 5.37 mmol) was added. After 40 min, the mixture was concentrated, and the residue was dissolved in DCM, washed with water and brine, and dried and concentrated to provide a white solid. This material was dissolved in DCM (10 mL) and treated with TFA (10 mL) and stirred for a few minutes at rt, then was treated with triethylsilane (6.40 mL, 40.1 mmol) and stirred at rt for 2.5 h. The mixture was concentrated and the residue was dissolved in DCM, washed with NaHCO3 (aq) and water. The organic phase was dried and concentrated. The residue was purified by column chromatography (eluting with hexane-EtOAc) to provide 2-(3-bromo-2-methylphenyl)-6-tert-butylisoindolin-1-one (Intermediate 4-3, 134 mg, 28%). 1H NMR (400 MHz, chloroform-d) δ 7.99 (1 H, d, J=1.32 Hz), 7.68 (1 H, dd, J=7.91, 1.76 Hz), 7.60 (1 H, dd, J=7.69, 1.10 Hz), 7.45 (1 H, d, J=7.91 Hz), 7.19-7.23 (1 H, m), 7.15 (1 H, t, J=7.69 Hz), 4.68 (2 H, s), 2.31 (3 H, s), 1.39 (9 H, s). Mass spectrum m/z 358, 360 (M+H)+. Also isolated was 2-(3-bromo-2-methylphenyl)-5-tert-butylisoindolin-1-one (Intermediate 4-4, 250 mg, 52%). 1H NMR (400 MHz, chloroform-d) δ 7.88 (1 H, d, J=7.91 Hz), 7.59 (2 H, dd, J=8.13, 2.86 Hz), 7.53 (1 H, s), 7.20-7.23 (1 H, m), 7.12-7.17 (1 H, m), 4.69 (2 H, s), 2.31 (3 H, s), 1.40 (9 H, s). Mass spectrum m/z 358, 260 (M+H)+.
