Methanol → Methyl {(2S,4R)-1-[(1S)-5-(benzyloxy)-4-methyl-1-(3,3,3-trifluoropropyl)pent-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate

Participants

Reaction Conditions

Reaction Steps

A mixture of (+)-methyl {(2S,4R)-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Intermediate 2, 440 mg, 1.460 mmol), {[(2-methylbut-3-yn-1-yl)oxy]methyl}benzene (509 mg, 2.92 mmol), 4,4,4-trifluorobutyraldehyde (368 mg, 2.92 mmol) and gold(III) bromide (63.8 mg, 0.146 mmol) were combined in water (1.5 ml) in a 5 ml microwave vial. The vial was sealed and the mixture was stirred and heated at 70° C. in the microwave. After cooling to RT, the mixture was diluted with MeOH and then loaded on to a SCX cartridge (2 g). The cartridge was washed with MeOH (5×10 ml), then the product was eluted with 2N NH3 in MeOH (5×10 ml). The NH3/MeOH fractions were combined and evaporated. The residue was partitioned between EtOAc/H2O. The aqueous layer was extracted with EtOAc (×3). The combined extracts were washed with brine (×1), dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography (silica, 5-10% EtOAc/isohexane) to give the title compound (562 mg, mixture of diasteromers) as a colourless oil. M/Z 584 (MH+).

Provenance & Evidence