Chlorotrimethylsilane → Tert-butyl 4-(2-bromoacetyl)-3-methylpiperidine-1-carboxylate

Temperature

0 °C

To a cooled (−78° C.) solution of LDA (5.69 mL, 11.4 mmol) in THF (100 mL) was added dropwise over 40 minutes a solution of tert-butyl 4-acetyl-3-methylpiperidine-1-carboxylate (2.29 g, 9.48 mmol) in THF (40 mL). After an additional 25 minutes, chlorotrimethylsilane (2.41 mL, 18.9 mmol) was added, dropwise over 20 minutes. After stirring for 1 hour the reaction was poured into 600 mL saturated sodium bicarbonate and extracted with ether (2×400 mL). The combined ether layers were washed with brine, dried, filtered, and concentrated. The crude material was dissolved in 500 mL THF, cooled to 0° C., and treated with sodium bicarbonate (1.20 g, 14.2 mmol), followed by NBS (1.69 g, 9.48 mmol). The reaction was warmed to ambient temperature while stirring for 90 minutes, then poured into 400 mL of saturated sodium bicarbonate solution and extracted with Et2O. The combined organic layers were washed with saturated NaHCO3, brine, dried, and concentrated to give the title compound (3.35 g, 110% yield).

1. extractionextracted with ether (2×400 mL)
2. washThe combined ether layers were washed with brine
3. customdried
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe crude material was dissolved in 500 mL THF
7. temperatureThe reaction was warmed to ambient temperature
8. stirringwhile stirring for 90 minutes
9. extractionextracted with Et2O
10. washThe combined organic layers were washed with saturated NaHCO3, brine
11. customdried
12. concentrationconcentrated

ORD record

ord-e440ff0dbbc642fe963318186be2e8e3

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362037B2