Sodium borohydride → 2-Methoxy-4-[4-(1-piperidyl)-1-piperidyl]aniline

Participants

Reaction Steps

To 1′-[3-(methyloxy)-4-nitrophenyl]-1,4′-bipiperidine (47.9 g, 150 mmol) and nickel(II) chloride hexahydrate (17.8 g, 75.0 mmol) in MeOH (600 mL) and THF (300 mL) cooled to 0° C. was added NaBH4 (˜30 g, ˜750 mmol) at such a rate to control the foaming which occurred. NaBH4 was added until the yellow color disappeared from the foam (TLC confirms consumption of starting material). The mixture was rotovaped down and placed on the high vacuum overnight. EtOAc (1000 mL) was added to the solid and the slurry was stirred for 3 h. The mixture was filtered through a pad of celite, rinsing with generous amounts of EtOAc. The filtrate was washed with 0.1N NaOH (2×1000 mL), dried (MgSO4), filtered, and rotovaped down to give the title compound (38.3 g, 133 mmol, 89%) as a pink solid. 1H NMR (400 MHz, CDCl3) δ 6.60 (d, J=8.4 Hz, 1H), 6.49 (d, J=2.4 Hz, 1H), 6.38 (dd, J=8.4, 2.4 Hz, 1H), 3.80 (s, 3H), 3.52-3.45 (m, 4H), 2.61-2.47 (m, 6H), 2.36-2.27 (m, 1H), 1.90-1.63 (m, 4H), 1.61-1.52 (m, 4H), 1.45-1.36 (m, 2H).

Provenance & Evidence