Chlorotrimethylsilane → Benzyl 3-fluoro-4-oxopiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 10.0 g (43 mmol) of benzyl-4-oxo-1-piperidinecarboxylate in 25 mL of DMF was added 14.3 mL (103 mmol) of triethylamine and then 6.53 mL (52 mmol) of TMSCl. The reaction was heated at 80° C. overnight, cooled to room temperature, and then dumped into hexanes in a separatory funnel. The mixture was partitioned with saturated aqueous NaHCO3, separated, washed with brine, dried over MgSO4 and concentrated by rotary evaporation. The residue was dissolved in 500 mL of CH3CN and treated with 16.7 g (47 mmol) of Selectfluor. After 90 min the reaction was concentrated to about half the original volume, partitioned between EtOAc and brine, separated, dried over MgSO4, filtered, and concentrated by rotary evaporation. The residue was loaded onto a silica gel column and eluted with EtOAc/hexanes to provide 2-2 as a colorless oil.

Provenance & Evidence