tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-hydroxypiperidine-1-carboxylate

Temperature

0 °C

tert-Butyl 4-oxo-1-piperidinecarboxylate (20 g, 100.4 mmol) was dissolved in methanol (250 mL) then cooled to 0° C. and sodium borohydride (3.8 g, 100.4 mmol) was added over 10 min. The reaction mixture was warmed from 0° C. to room temperature. After 4 hours, the reaction was concentrated under reduced pressure and the remaining syrup was dissolved in 3:1 dichloromethane/isopropanol (400 mL). The organic layer was washed with aqueous 1N sodium hydroxide (200 mL). The aqueous layer was then extracted with 3:1 dichloromethane/isopropanol (3×150 mL). The organic layers were washed with brine (400 mL) then dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield tert-butyl 4-hydroxy-1-piperidinecarboxylate as a light yellow syrup (20 g, 100.4 mmol). 1H NMR (d6-DMSO): δ 1.21-1.28 (m, 2H), 1.38 (s, 9H), 1.65-1.69 (m, 2H), 2.94-2.96 (m, 2H), 3.59-3.68 (m, 3H), 4.68 (d, 1H).

1. temperatureThe reaction mixture was warmed from 0° C. to room temperature
2. concentrationthe reaction was concentrated under reduced pressure
3. dissolutionthe remaining syrup was dissolved in 3:1 dichloromethane/isopropanol (400 mL)
4. washThe organic layer was washed with aqueous 1N sodium hydroxide (200 mL)
5. extractionThe aqueous layer was then extracted with 3:1 dichloromethane/isopropanol (3×150 mL)
6. washThe organic layers were washed with brine (400 mL)
7. dry with materialthen dried over anhydrous sodium sulfate
8. concentrationconcentrated under reduced pressure

ORD record

ord-a66d7379ccae4065b6ba08cf6b26d859

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06660744B1