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 to afford crude TMS-enol ether, which was then redissolved in 500 mL THF and 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 allowed to warm to ambient temperature while stirring for 90 minutes at which point it was poured into 400 mL of saturated sodium bicarbonate solution and extracted with Et2O and the combined organic layers were washed with saturated NaHCO3, brine, dried, and concentrated to give the title compound (3.35 g, 110% yield) as an orange oil.

1. extractionextracted with ether (2×400 mL)
2. washThe combined ether layers were washed with brine
3. customdried
4. filtrationfiltered
5. concentrationconcentrated
6. customto afford crude TMS-enol ether, which
7. temperatureto warm to ambient temperature
8. stirringwhile stirring for 90 minutes at which point it
9. extractionextracted with Et2O
10. washthe combined organic layers were washed with saturated NaHCO3, brine
11. customdried
12. concentrationconcentrated

ORD record

ord-a4b692682ae346fb8ab698c9ce1c33a8

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354540B2