Chlorotrimethylsilane → 1-tert-Butyloxycarbonyl-3-bromo-4-oxopiperidine

Participants

Reaction Steps

Chlorotrimethylsilane (5.6 ml, 44 mmol) was added slowly to a solution of tert-butyl 4-oxopiperidine-1-carboxylate (commercial, 8 g, 40 mmol), triethylamine (12.3 ml, 88 mmol) and DMF (40 ml) at room temperature. The resultant solution was heated to 75° C. and stirred overnight under nitrogen. The reaction mixture was cooled to room temperature and then in an ice bath. Cold hexane (250 ml) was added slowly to the reaction mixture followed by cold (saturated) aqueous sodium bicarbonate (50 ml). The organic phase was separated and washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude silyl enolether was dissolved in THF (15 ml) and cooled to 0° C. N-Bromosuccinimide (7.1 g, 40 mmol) was dissolved in THF (120 ml) and added slowly (45 min.) to the reaction mixture. The resultant mixture was allowed to slowly warm to room temperature and stirred overnight. The reaction mixture was concentrated under reduced pressure. The crude residue was purified by flash chromatography (hexanes/ethyl acetate, 5:1) to provide the title compound as a white solid (11 g).

Provenance & Evidence