3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-bromobenzonitrile (0.400 g, 1.125 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.130 g, 0.112 mmol) were combined in THF (7 mL) and treated with an apparent mixture of diisopropylzinc and di-n-propylzinc (1 M in toluene, Aldrich 568112) (2.250 mL, 2.250 mmol) with stirring under an inert atmosphere. The reaction mixture was heated to 70° C. and stirred for 2 h. The reaction mixture was concentrated to dryness and partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was isolated, dried over MgSO4, filtered and concentrated to dryness. The residue was purified on 40 g silica gel eluted successively with EtOAc and 10% CH3OH/DCM to give a mixture of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(1-methylethyl)benzonitrile and 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-propylbenzonitrile (1:6 ratio) (0.198 g, 0.621 mmol, 55.2% yield) as a clear oil. Diagnostic peaks in the aliphatic region of the NMR are as indicated below and were found to be in a ratio of ˜1:6, 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(1-methylethyl)benzonitrile to 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-propylbenzonitrile. 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(1-methylethyl)benzonitrile: 1H NMR (400 MHz, DMSO-d6) δ ppm 2.95 (spt, J=6.82 Hz, 1H), 1.19 (d, J=6.87 Hz, 6H). 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-propylbenzonitrile: 1H NMR (400 MHz, DMSO-d6) δ ppm 2.58 (t, J=7.55 Hz, 2H), 1.49-1.63 (m, 2H), 0.85 (t, J=7.33 Hz, 3H). LC-MS (ES−) m/z 317.12, 319.14 [M−1]. LC-MS (ES+) m/z 318.99, 320.99 [M+H].
