Ethyl propiolate → (2S,3R)-3-(Ethoxycarbonylethynyl)-3-hydroxy-2-phenylpiperidine

Participants

Reaction Steps

A solution of n-butyllithium (55.4 ml, 1.4 M in hexanes, 77.6 mmol) was added dropwise to a stirred solution of ethyl propiolate (7.9 ml, 77.7 mmol) in tetrahydrofuran (200 ml), keeping the temperature of the reaction below −65° C. The mixture was stirred for 10 min and a solution of (2S)-2-phenyl-3-piperidone in tetrahydrofuran (50 ml) added dropwise at −72° C. over 15 min. The reaction mixture was stirred at this temperature for 40 min, quenched with acetic acid (10 ml) and warm up to room temperature. Solvent was removed in vacuo. The residue was treated with saturated aqueous NaHCO3 (200 ml) and extracted with ethyl acetate (3×100 ml). The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (210 g, hexane:diethyl ether 5-40%) to afford the product (11.9 g, 83%, 96% ee) as a colourless oil.

Provenance & Evidence