Benzyl Alcohol → Benzyl [trans-1-[bis(4-methoxyphenyl)methyl]-6-oxo-4-(2,4,5-trifluorophenyl)piperidin-3-yl]carbamate

Participants

Reaction Steps

To 5.4 g (9.7 mmol) of the product of Step E in 60 mL of toluene was added 1.8 mL (12 mmol) of triethylamine followed by 2.8 mL (13 mmol) of diphenylphosphoryl azide. After stirring at ambient temperature for 30 min, the reaction mixture was warmed to 70° C. for 30 min, then slowly heated to reflux for an additional 2 h. The reaction mixture was cooled to ambient temperature, 3.2 g (30 mmol) of benzyl alcohol was added, and the reaction mixture was heated to reflux for 5 h. The solution was then cooled to ambient temperature and quenched with 1N aqueous hydrochloric acid (100 mL) The resulting mixture was extracted with three 150-mL portions of ethyl acetate, the organic phases combined and washed sequentially with 1N hydrochloric acid, saturated aqueous sodium bicarbonate solution, and saturated aqueous brine (100 mL each). The organic phase was then dried over magnesium sulfate, filtered, and evaporated in vacuo to yield a viscous crude oil. The crude material was purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 40% ethyl acetate/hexanes gradient) to give the title compound as a colorless crystalline solid. LC/MS 605.6 (M+1).

Provenance & Evidence