tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-butyl-4-hydroxy-1-piperidinecarboxylate

To a solution of n-butyl lithium (16.06 mL, 40.2 mmol, 2.5 M in hexanes) at −78° C., was drop-wise added a solution of N-Boc-4-piperidone (4.0 g, 20.1 mmol) in ether (10 mL). The resulting solution was allowed to warm to room temperature and stirred for one additional hour. The solution was cooled to 0° C. before being quenched by the drop-wise addition of saturated aqueous ammonium chloride (30 mL), and extracted with ethyl acetate (2×30 mL). The combined organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to give the crude product as a yellow oil, which was then purified by silica chromatography on a Biotage (0-50% of EtOAc/Hexanes) to give the title compound as a colorless oil (1.66 g, still contaminated with the starting material ketone). This mixture was used in the next step without further purification.

1. temperatureThe solution was cooled to 0° C.
2. custombefore being quenched by the drop-wise addition of saturated aqueous ammonium chloride (30 mL)
3. extractionextracted with ethyl acetate (2×30 mL)
4. dry with materialThe combined organic layer was then dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto give the crude product as a yellow oil, which
8. customwas then purified by silica chromatography on a Biotage (0-50% of EtOAc/Hexanes)

ORD record

ord-8167355f6ba84345881dadea454ddf21

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08114894B2