2-Bromo-5-fluorobenzotrifluoride → (R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine

Participants

Reaction Conditions

Reaction Steps

(R)-2-methyl-piperazine (3.5 g, 34.9 mmol), 2-bromo-5-fluoro benzotrifluoride (7.74 g, 31.7 mmol), BINAP (0.59 g, 0.95 mmol), tBuONa (4.58 g, 47.65 mmol) and Pd2(dba)3 (0.29 g, 0.32 mmol) were mixed in the flask and purged with N2. Anhydrous toluene (50 mL) was added and purged with N2 again. The resulting mixture was heated in an oil bath at 100° C. under N2 for 3 hours. The mixture was cooled to room temperature, diluted with dichloromethane (150 mL), washed with H2O (30 mL) first, then washed with saturated brine (30 mL). The combined organic layer was dried over Na2SO4, concentrated down under reduced pressure to give a brown color liquid as crude. The crude product was purified on silica gel column eluted with 5-10% MeOH in DCM to give (3R)-1-[4-fluoro-2-(trifluoromethyl)phenyl]-3-methylpiperazine as a light yellow oil (6.85 g, 82%).

Provenance & Evidence