Piperidine → 1-(4-Methoxy-2-trifluoromethyl-phenyl)-piperidine

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-Bromo-4-methoxy-2-trifluoromethyl-benzene (500 mg, 1.961 mmol) in 1,4-dioxane (8 mL) is added sequentially: piperidine (2 eq., 3.921 mmol, 0.41 mL), Pd2dba3 (2 mol %, 0.039 mmol, 36 mg), KtOBu (1.5 eq., 2.941 mmol, 330 mg) and 1,3-(Bis(2,6-di-iso-propylphenyl)-imidazolium chloride (iPrHCl, 4 mol %, 0.078 mmol, 33 mg). The resulting reaction mixture is heated in a sealed tube at 150° C. oil bath for 12 hours. After cooling to room temperature, the reaction mixture is concentrated. The residue obtained is partially purified by silica gel chromatography (9:1 hexanes/EtOAc) to give crude 1-(4-Methoxy-2-trifluoromethyl-phenyl)-piperidine.

Provenance & Evidence