(Trifluoromethyl)trimethylsilane → Tert-butyl 4-hydroxy-4-(trifluoromethyl)piperidine-1-carboxylate

Tetrabutylammonium fluoride (50 mg, 1M solution in tetrahydrofuran) was added to an ice-cooled solution of (trifluoromethyl)trimethylsilane (2.1 g, 15 mmol) and tert-butyl 4-oxo-1-piperidinecarboxylate (2 g, 10 mmol) in tetrahydrofuran (20 ml), and the reaction stirred at room temperature for 18 hours. The mixture was concentrated under reduced pressure, the residue suspended in ethyl acetate, hydrochloric acid (20 ml, 1N) was added, the mixture stirred for an hour, and then neutralised using sodium bicarbonate. The solution was washed with water, then brine, dried (MgSO4) and evaporated under reduced pressure to give a gum. This was purified by column chromatography on silica gel using an elution gradient of dichloromethane:methanol (100:0 to 98:2) to afford the title compound, 1.94 g.

1. concentrationThe mixture was concentrated under reduced pressure
2. additionhydrochloric acid (20 ml, 1N) was added
3. stirringthe mixture stirred for an hour
4. washThe solution was washed with water
5. dry with materialbrine, dried (MgSO4)
6. customevaporated under reduced pressure
7. customto give a gum
8. customThis was purified by column chromatography on silica gel using an elution gradient of dichloromethane:methanol (100:0 to 98:2)

ORD record

ord-81dce53ab7e5409aa85e12d3ea7d318b

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07060836B2