Toluene → (R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine

Participants

Reaction Conditions

Reaction Steps

(R)-2-methyl-piperazine (3.88 g, 38.70 mmol), 2-bromo, 5-fluoro benzotrifluoride (8.55 g, 35.18 mmol), tris(dibenzylidineacetone)dipalladium (0) (32.0 mg g, 0.35 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (657.0 mg, 1.06 mmol) and sodium tert-butoxide (5.07 g, 52.77 mmol) were charged to a reaction flask. Toluene (40 mL) was introduced under nitrogen atmosphere and the reaction mixture was heated up at 110° C. for 5.0 hours. Reaction was complete as determined by TLC. The reaction mixture was diluted with dichloromethane, washed with water, saturated brine then dried over MgSO4 and concentrated. The crude product was purified via flash column chromatography to yield (R)-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-methylpiperazine as a light brown oil (3.1 g, 33.6% yield).

Provenance & Evidence