Acetic Acid → tert-Butyl 4-(2-hydroxyanilino)piperidine-1-carboxylate

Participants

Reaction Steps

A solution of 2-hydroxyaniline (5.0 g, 46 mmol), N-t-butyloxycarbonyl-4-piperidinone (9.05 g, 46 mmol) and HOAc (5.7 mL, 100 mmol) in dry toluene (250 mL) was refluxed with azeotropic removal of water for 24 h. The solution was cooled to ambient temperature and to it was added NaCNBH3 (5.8 g, 92 mmol). The resulting mixture was stirred at ambient temperature for 24 h. EtOAc (250 mL) was added and the solution was washed with saturated aqueous NaHCO3 (4×100 mL). The organic phase was dried (MgSO4), filtered, and the solvents were removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using a gradient elution of 15-25% EtOAc-hexanes. 1-t-Butyloxycarbonyl-4-(2-hydroxyphenylamino)piperidine was obtained as a solid (45% yield).

Provenance & Evidence