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

Participants

Reaction Steps

A mixture of 6.0 g N-t-butyloxycarbonyl-4-piperidone, 3.3 g of 2-aminophenol, 25 mL of 1,2-dichloroethane, 25 mL of glacial acetic acid, and 500 mg powdered 4 Å molecular sieves was stirred under inert atmosphere. After 30 min, 6.4 g sodium triacetoxyborohydride was added stirring was continued for 38 h. The reaction mixture was poured into 400 mL ethyl acetate and 200 mL saturated aqueous NaHCO3 and the layers separated. The organic layer was washed with brine (2×100 mL), dried over MgSO4, filtered and concentrated under reduced pressure. Chromatography of the crude product on silica gel, eluting with a gradient of 1-3% methanol/methylene chloride containing 0.5% concentrated NH4OH gave 1-t-butyloxycarbonyl-4-(2-hydroxyphenylamino)piperidine as an orange foam.

Provenance & Evidence