Acetic Acid → tert-Butyl 4-hydroxy-[1,4'-bipiperidine]-1'-carboxylate

Participants

Reaction Steps

A mixture of 1,1-dimethylethyl 4-oxo-1-piperidinecarboxylate (3.15 g, 15.8 mmol), 4-piperidinol (1.0 g, 9.88 mmol), and acetic acid (0.8 mL) in methylene chloride (30 mL) was stirred for 3 h at room temperature. Sodium triacetoxyborohydride (3.35 g, 15.8 mmol) was added and the mixture was stirred at room temperature for 18 h. The solvent was removed under reduced pressure, and the residue was dissolved in methylene chloride and washed with 1N HCl. The aqueous phase was extracted with ether (3×10 mL) and adjusted to pH 9-10 with 1N NaOH. The basic aqueous mixture was extracted with methylene chloride (3×10 mL). The combined organic extracts were concentrated in vacuo to afford 1,1-dimethylethyl 4-hydroxy-1,4′-bipiperidine-1′-carboxylate (1.1 g, 39% yield). This material was used in the next step without further purification.

Provenance & Evidence