Benzylamine → 2-Benzyl-5-fluoroisoindoline

Participants

Reaction Steps

A solution of benzylamine (64.3 ml) and triethylamine (164 ml) in toluene (1 L) was added to 1,2-bis(bromomethyl)-4-fluorobenzene (164.1 g) (J. Org. Chem., 1988, 53, 1775-9). This mixture was heated to reflux for 4 h under argon. The reaction mixture was then filtered and the solid was washed with toluene (3×150 ml). The filtrate was evaporated in vacuo and the residue dissolved in dichloromethane (1 L). This solution was washed successively with a saturated solution of potassium carbonate (1 L) and water (0.5 L). The organic extract was dried (MgSO4), concentrated to a volume of 0.5 L and cooled in ice. The unwanted precipitate was filtered off and the filtrate evaporated to a residue which was purified by chromatography over silica gel eluting with a gradient of dichloromethane/ethyl acetate to give the title compound (D7) as an oil (49.3 g). MS electrospray (+ion) 228 (MH+). 1H NMR δ (CDCl3): 7.24-7.42 (5H, m), 7.07-7.12 (1H, m), 6.82-6.89 (2H, m), 3.89 (6H, br, s).

Provenance & Evidence