Sulfuric Acid → C-[4-(4-Iodo-phenyl)-1-(3,3,3-trifluoro-propyl)-piperidin-4-yl]-methylamine

Participants

Reaction Conditions

Reaction Steps

To a solution of LiAlH4 (1 M in THF, 6.5 mL, 6.5 mmol, 3.5 eq.) at 0° C. was added H2SO4 (0.31 mL, 5.58 mmol, 3 eq.) in a drop-wise fashion. The resulting white precipitate was stirred at 25° C. for 1 h. A solution of 4-(4-iodo-phenyl)-1-(3,3,3-trifluoro-propyl)-piperidine-4-carbonitrile (0.761 g, 1.86 mmol, 1 eq.) in THF (6 mL) was added and the mixture was heated at 40° C. for 3 h. The reaction was cooled to 0° C., quenched by addition of H2O (0.25 mL), 1 N NaOH (0.5 mL) and H2O (0.75 mL). The resulting slurry was filtered through a pad of celite, washed with EtOAc and then concentrated by rotary evaporation to give a yellow oil which was purified by flash column chromatography by eluting with 1.5% MeOH/1% Et3N/CH2Cl2 to give the title compound C-[4-(4-Iodo-phenyl)-1-(3,3,3-trifluoro-propyl)-piperidin-4-yl]-methylamine as a pale foam (0.139 g, 0.337 mmol, 18%). 1H NMR (300 MHz, CDCl3): δ 7.80 (d, 2H), 7.18 (d, 2H), 3.78 (t, 1H), 2.86 (s, 2H), 2.74 (m, 2H), 2.62 (m, 2H), 2.30 (m, 4H+NH2), 1.94 (ddd, 2H), 1.78 (m, 1H); MS(ESI): 413.0 (M+1).

Provenance & Evidence