Acetic Acid → 8-bromo-1-methyl-2,3,4,5-tetrahydro-1H-benzo[b]azepine

Participants

Reaction Steps

To a solution of 8-bromo-2,3,4,5-tetrahydro-1H-benzo[b]azepine (D50) (395 mg, 1.747 mmol) in 25 mL of MeOH and acetic acid (1 mL, 17.47 mmol) was added formaldehyde (37% aq solution) (0.780 mL, 10.48 mmol) and the reaction mixture stirred for 30 minutes followed by the addition of a solution of sodium cyanoborohydride (878 mg, 13.98 mmol) in MeOH (10 mL). The reaction mixture was stirred at RT for 1 hour, then basified by the slow addition of sodium hydrogen carbonate aqueous solution (ca. 50 mL). The aqueous layer was extracted with DCM (3×50 mL), the organic layers were combined, passed through a hydrophobic frit and concentrated. The residue was purified by column chromatography on silica gel, eluting with a gradient of 0-5% ethyl acetate in cyclohexane to afford the title compound (357 mg). LCMS (A): m/z (M+H)+ 240/242, C11H14BrN requires 239/241 (acidic).

Provenance & Evidence