Formaldehyde → 1-(3-Bromophenyl)-4-methylpiperazine

Participants

Reaction Steps

To a solution of 1-(3-bromo-phenyl)-piperazine (about 1 g) and acetic acid (about 0.4 mL) in methanol (about 25 mL) is added 37% formaldehyde in water/methanol (about 56.7:37:6.3, water:formaldehyde:methanol; about 5 mL). The mixture is stirred at room temperature for about 18 hours. The suspension is cooled to about 5° C. in an ice/water bath and sodium cyanoborohydride (about 5 g) is added in small portions. The mixture is stirred and warmed to room temperature for about 18 hours. The mixture is slowly poured into saturated aqueous ammonium chloride (about 200 mL) and stirred for about 1 hour. The mixture is extracted with dichloromethane (3× about 75 mL). The combined organic layers are dried over magnesium sulfate, filtered and evaporated. The material is placed under high vacuum for about 18 hours to yield 1-(3-bromo-phenyl)-4-methyl-piperazine as a pale yellow oil (about 1 g). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.10 (dd, J=8.2, 8.2 Hz, 1H), 7.04 (dd, J=2.1, 2.1 Hz, 1H), 6.95 (ddd, J=7.8, 1.7, 0.7 Hz, 1H), 6.83 (ddd, J=8.3, 2.4, 0.6 Hz, 1H), 3.23-3.18 (m, 4H), 2.58-2.54 (m, 4H), 2.35 (s, 3H). MS=255, 257 (MH)+.

Provenance & Evidence