Ethanol → 4-Bromo-2-methylisoindolin-1-one

Participants

Reaction Steps

An 8M solution of methylamine in ethanol (10 mL, 80 mmol) was added to a solution of methyl 3-Bromo-2-(bromomethyl)benzoate in THF (30 mL) and allowed to stir for 2 h. The reaction mixture was concentrated to dryness and the residue was triturated with water. The solids produced were collected by filtration and dried to afford 4-bromo-2-methyl-2,3-dihydroisoindol-1-one which used immediately in the next step. To a cold suspension of 4-bromo-2-methyl-2,3-dihydroisoindol-1-one (60 g, 265 mmol) in concentrated sulfuric acid (60 mL) was added pre-cooled mixture of conc. nitric acid (12.5 mL, 265 mmol) and conc. sulfuric acid (60 mL) over 20 min. The reaction mixture was stirred for 30 min at 0° C. and 2 h at room temperature. The reaction mixture was poured into an ice-water mixture (300 mL) and the precipitate that formed was collected by filtration and washed with water (3×100 mL). The solids were suspended in isopropanol (200 mL) and heated on a steam bath for 10 minutes. The mixture was cooled and the solid was collected by filtration and air dried to afford 53 g of the title compound (74%). 1H NMR (CDCl3, 300 MHz) δ 3.22 (s, 3H), 4.36 (s, 2H), 7.67 (d, J=8.4 Hz, 1H), 7.78 (d, J=8.4 Hz, 1H).

Provenance & Evidence