Formaldehyde → (+/-)-3'-(1-((1-Methyl-4-phenylpiperidin-4-yl)methoxy)ethyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrile

Participants

Reaction Steps

To a suspension of (±)-3′-(1-((4-phenylpiperidin-4-yl)methoxy)ethyl)-5′-(trifluoromethyl)biphenyl-4-carbonitrile (15 mg, 0.032 mmol) and sodium cyanoborohydride (10.2 mg, 0.16 mmol) in acetonitrile (1 mL) at 0° C. was added formalin (0.1 mL, 3.6 mmol). The ice bath was removed and stirring continued for 1 h. The reaction was concentrated and loaded onto an SCX cartridge in methanol. The cartridge was flushed with several volumes of methanol which was discarded. The product was eluted with 2 M ammonia in methanol and concentrated to give 13 mg (84%) as a colorless film. 1H NMR (500 MHz, CDCl3) δ ppm 7.74 (m, 2H), 7.64 (s, 1H), 7.56 (m, 2H), 7.37 (s, 2H), 7.22-7.35 (m, 5H), 7.16 (m, 1H), 4.29 (q, J=6.4 Hz, 1H), 3.32 (d, J=8.9 Hz, 1H), 3.25 (d, J=8.9 Hz, 1H), 2.61 (m, 2H), 2.11-2.35 (m, 7H), 1.95-2.10 (m, 2H), 1.34 (m, 3H). Mass spec.: 479.30 (MH)+. Accurate mass spec.: m/z 479.2300 [MH]+, Δ=2.1 ppm.

Provenance & Evidence