4-Bromoanisole → 1-(3-Bromophenyl)-1-(4-methoxyphenyl)-1H-isoindol-3-amine

Participants

Reaction Conditions

Reaction Steps

To a −78° C. solution of 4-bromoanisole (0.45 mL, 3.6 mmol) in tetrahydrofuran (15 mL) was n-butyllithium (2.5 M in hexane, 1.3 mL, 3.3 mmol) added, after 0.5 h a solution of N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (Scheme #5, N) (1.2 g, 3.0 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was stirred at −78° C. for 3 h and then quenched by addition of water. Ethyl acetate was added and the mixture was washed with water and brine, dried over magnesium sulfate and concentrated. The residue was dissolved in methanol (25 mL) and treated with hydrochloric acid (2 M in diethyl ether, 3.0 mL, 6.0 mml) over night. The reaction mixture was concentrated and then partitioned between aqueous saturated sodium bicarbonate and chloroform, the organic phase was dried over magnesium sulfate and concentrated. Purification by column chromatography using a gradient of methanol in dichloromethane gave the title compound (0.70 g, 59%). 1H NMR (CDCl3) δ 7.57-7.48 (m, 3 H), 7.47-7.41 (m, 1 H), 7.39-7.32 (m, 2 H), 7.32-7.28 (m, 1 H), 7.26-7.20 (m, 2 H), 7.10 (t, J=7.83 Hz, 1 H), 6.83-6.77 (m, 2 H), 5.86 (br s, 2 H), 3.75 (s, 3 H); MS (AP) m/z 393, 395 [M+1]+.

Provenance & Evidence