Dimethylformamide → 3-(2-Benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-benzonitrile

Participants

Reaction Conditions

Reaction Steps

Trifluoro-methanesulfonic acid 3-(2-benzyl-2-aza-bicyclo[3.3.1]non-5-yl)-phenyl ester (5.00 g, 11.4 mmol) and zinc cyanide (1.47 g, 12.5 mmol) were combined in DMF (110 ml), degassed (evac./N2 purge 3×) then charged with tetrakis(triphenylphosphine) palladium (0) (1.8 g, 1.60 mmol). The resulting reaction mixture was heated to 85° C. in an oil bath for 6 h. Upon cooling to room temperature, the reaction mixture was filtered through a Celite pad and rinsed with EtOAc (200 ml). The filtrate was washed with water and saturated aqueous NaCl solution (1×200 ml each), dried over Na2SO4, filtered, and concentrated and chromatographed on silica gel eluting with 50% EtOAc/hexanes to provide an oil (1.95 g, 54%). (TLC 50% EtOAc/hexanes Rf 0.28); 1H NMR (400 MHz, CDCl3) δ 7.49–7.52 (m, 2H), 7.45–7.48 (m, 3H), 7.35–7.39 (m, 2H), 7.10–7.14 (m, 1H), 7.00–7.02 (m, 1H), 3.98 (ABq, □AB=48.9 Hz, J=13.0 Hz, 2H), 3.31–3.33 (m, 1H), 3.16–3.21 (m, 2H), 2.21–2.25 (m, 2H), 1.95–2.07 (m, 4H), 1.76–1.80 (m, 2H), 1.41–1.59 (m, 2H); APCI MS m/z 317.2 (M+1)+.

Provenance & Evidence