Trifluoroacetic acid → 2-Cyanoquinuclidine

To a solution of tert-butyl 4-{2-cyano-2-[(methylsulfonyl)oxy]ethyl}piperidine-1-carboxylate (80.0 g) in dichloromethane (200 mL) was added a solution of trifluoroacetic acid (137.0 g) in dichloromethane (200 mL), and the reaction system was stirred at room temperature overnight. The reaction system was concentrated, acetonitrile (200 mL) was added to the residue, and triethylamine (98.0 g) was slowly added at 0° C. The mixture was concentrated, the residue was diluted with dichloromethane, and the mixture was washed with brine, and dried over anhydrous sodium sulfate. Insoluble material was removed by filtration, and the filtrate was concentrated. The residue was purified by flash silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (13.0 g) as a yellow oil.

1. concentrationThe reaction system was concentrated
2. additionacetonitrile (200 mL) was added to the residue, and triethylamine (98.0 g)
3. additionwas slowly added at 0° C
4. concentrationThe mixture was concentrated
5. additionthe residue was diluted with dichloromethane
6. washthe mixture was washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. customInsoluble material was removed by filtration
9. concentrationthe filtrate was concentrated
10. customThe residue was purified by flash silica gel column chromatography (ethyl acetate/petroleum ether)

ORD record

ord-f8a30b678c35403aa1c0f6d8f23b908d

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388195B2