Dimethylformamide → HCID 69430458, compound

Participants

Reaction Conditions

Reaction Steps

3-Benzyl-8-(3-bromo-phenyl)-8-methoxy-3-aza-bicyclo[3.2.1]octane (2.17 g, 5.62 mmol) and zinc cyanide (0.99 g, 8.43 mmol) were combined in DMF (30 ml), degassed (evac./N2 purge 3×) then charged with tetrakis(triphenylphosphine) palladium (0) (3.24 g, 2.81 mmol). The resulting reaction mixture was heated to 85° C. in an oil bath for 5 h. Upon cooling to room temperature, the reaction mixture was filtered through a Celite pad and rinsed with EtOAc. The filtrate was extracted with 1 N HCl (2×50 ml) then neutralized to pH 8 with 1 N NaOH and saturated aqueous NaHCO3, causing an emulsion to form. The product was extracted with EtOAc (3×100 ml), washed with saturated aqueous NaCl solution (2×100 ml), dried over Na2SO4, filtered, and concentrated. The resulting crude product was dissolved in ether (100 ml) then washed with 50% saturated aqueous NaCl solution (4×100 ml), dried over Na2SO4, filtered and concentrated to a yellow oil (1.40 g, 75%). (TLC 20% EtOAc/hexanes Rf 0.40); 1H NMR (400 MHz, CDCl3) δ 7.69 (m, 2H), 7.56 (d, J=7.9 Hz, 1H), 7.45 (t, J=7.9 Hz, 1H), 7.36–7.20 (m, 5H), 3.58 (br s, 2H), 2.82 (s, 3H), 2.75 (d, J=10.3 Hz, 2H), 2.54 (br d, J=10.3 Hz, 2H), 2.43 (br s, 2H), 1.83 (d, J=8.1 Hz, 2H), 1.33 (m, 2H); APCI MS m/z 333.2 (M+1)+.

Provenance & Evidence