Toluene → 1-[4-(Phenylmethoxy)phenyl]-4-[4-(trifluoromethoxy)phenoxy]piperidine

Participants

Reaction Steps

4-[4-(Trifluoromethoxy)phenoxy]piperidine (26.1 g), benzyl 4-bromophenyl ether (26.3 g), palladium (II) acetate (22.4 mg), Tri-tert-butyl phosphonium tetraphenyl borate (52.3 mg), sodium tert-butoxide (10.6 g) and toluene (130 mL) were placed in a vessel and heated to reflux for 4 hr under Ar. The reaction mixture was then cooled to room temperature and water (260 mL) and ethyl acetate (260 mL) were added. The organic material was taken up in ethyl acetate. The organic layer was washed two times with water (260 mL×2). The organic layer was filtered to remove a harz and then the organic layer was condensed under reduced pressure to give 43.34 g (97.82% crude yield, 97.34% HPLC purity) of the pale yellow product. The crude product (43.3 g) and ethanol (433 mL) were placed in a vessel and heated until to dissolve and then the mixture was allowed to cool to 0° C. for 1 hr. The mixture was then filtered and the crystalline powder washed with cooled ethanol (43 mL) and then dried at 40° C. for 15 hr to afford 39.7 g (91.7% yield) of a pale yellow crystal target compound.

Provenance & Evidence