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

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).

1. customThe organic phase was separated
2. washwashed with brine
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. dissolutionThe crude silyl enolether was dissolved in THF (15 ml)
7. temperaturecooled to 0° C
8. additionadded slowly (45 min.) to the reaction mixture
9. temperatureto slowly warm to room temperature
10. stirringstirred overnight
11. concentrationThe reaction mixture was concentrated under reduced pressure
12. customThe crude residue was purified by flash chromatography (hexanes/ethyl acetate, 5:1)

ORD record

ord-424aed0b65454ed7b9195f4a2accc51a

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399489B2