Hydrochloric Acid → 8-(3-Amino-phenyl)-3-benzyl-3-aza-bicyclo[3.2.1]octan-8-ol

Participants

Reaction Conditions

Reaction Steps

3-Benzyl-8-(3-bromo-phenyl)-3-aza-bicyclo[3.2.1]octan-8-ol (4.69 g, 7.82 mmol) was dissolved in toluene (40 mL) in a flame dried RB flask. To this was added benzophenone imine (1.57 mL, 9.38 mmol), sodium t-butoxide (1.05 g, 11.0 mmol), then BINAP (racemic, 0.487 g, 0.782 mmol). The reaction was degassed (evac./N2 purged 3×) before adding palladium II acetate (0.175 g, 0.782 mmol), then heated to 100° C. in an oil bath under N2 overnight (or until judged complete by TLC). The imine was cooled to room temperature, treated with 6 N HCl (25 mL), and heated to 100° C. After 1 h, the reaction was cooled to room temperature, filtered through a Celite pad, rinsed with ether (50 mL) then water (50 mL). The filtrate was washed with ether (2×100 mL), then the aqueous layer was basified to pH 10 with 1 N NaOH, and saturated aqueous Na2CO3 solution. The product was extracted with EtOAc (3×100 mL), washed with saturated aqueous NaCl solution (1×100 mL), dried over Na2SO4, filtered through a Silica pad (2×3 in) eluted with 100% EtOAc and concentrated to an orange foam (2.34 g, 97%). (TLC 50% EtOAc/hexanes Rf 0.30); 1H NMR (400 MHz, CDCl3) δ 7.38–7.20 (m, 5H), 7.12 (t, J=7.9 Hz, 1H), 6.86 (d, J=7.9 Hz, 1H), 6.79 (s, 1H), 6.59 (m, 1H), 3.64–3.57 (m, 2H−NH2, 2H), 2.85 (d, J=9.9 Hz, 2H), 2.58 (m, 2H), 2.34 (br s, 2H), 1.77 (d, J=7.1 Hz, 2H), 1.43 (m, 2H); APCI MS m/z 309.2 (M+1)+.

Provenance & Evidence