Allyl bromide → 3-Allyl-6-methyl-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a cooled, stirred solution of lithium bis(trimethylsilyl)amide (1.0 M in THF, 2.0 mL, 2.0 mmol) in THF (10 mL) at −78° C., was added a solution of (5S,6R & 5R,6S)-6-methyl-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-2-one (0.50 g, 1.54 mmol) in THF (10 mL) dropwise, keeping the internal temperature of the reaction mixture below −65° C. The resulting mixture was stirred at −78° C. for 30 min, then a cold (−78° C.) solution of allyl bromide (0.242 g, 2.0 mmol) in THF (10 mL) was added dropwise, keeping the internal temperature of the reaction mixture below −65° C. The reaction mixture was allowed to warm slowly to ambient temperature and stirred for 18 h. The reaction was quenched by the addition of a saturated solution of sodium chloride (20 mL) and partitioned between water (50 mL) and EtOAc (200 mL). The organic layer was removed and the aqueous phase was extracted further with EtOAc (50 mL). The combined organic extracts were washed with brine, then dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanes:EtOAc—100:0 to 40:60, to give the title compound. MS: m/z=366.1 (M+1).

Provenance & Evidence