Ethyl 4-oxo-1-piperidinecarboxylate → Ethyl 4-cyano-4-(4-hydroxy-1-piperidyl)piperidine-1-carboxylate

Participants

Reaction Steps

To a stirred solution of 4-hydroxypiperidine (1.01 g, 10.0 mmol) and ethyl 4-oxopiperidine-1-carboxylate (1.71 g, 10.0 mmol) in 1,2-dichloroethane (25 mL) was added titanium isopropoxide (2.3 mL, 11.0 mmol), and the mixture was stirred at room temperature for 18 h. Then a 1.0 M solution of diethylaluminum cyanide (24.0 mL, 24.0 mmol) was added at room temperature, stirred for 24 h, and diluted with EtOAc. The reaction was quenched at 0° C. with saturated NaHCO3 (10 mL) and the mixture was further stirred for 2 h. The mixture was then filtered through Celite and the filtrate was concentrated in vacuo and purified by flash chromatography (ethyl acetate/hexane) to afford the title compound (2.45 g, 87%) as an oil. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.19 (t, J=7.08 Hz, 3H), 1.45-1.67 (m, 4H), 1.85 (d, J=10.16 Hz, 2H), 2.00 (d, J=12.89 Hz, 2H), 2.20-2.28 (m, 2H), 2.81-2.92 (m, 2H), 3.04-3.23 (m, 3H), 3.58-3.71 (m, 1H), 3.81-3.98 (m, 2H), 4.06 (q, J=7.08 Hz, 2H).

Provenance & Evidence