(2S)-1-tert-butoxycarbonyl-2-phenylpiperidin-3-one → (2S,3R)-1-tert-Butoxycarbonyl-3-hydroxy-3-(2-methylene-3-phenoxypropyl)-2-phenylpiperidine

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Reaction Steps

A tetrahydrofuran solution of 3-(chloromagnesio)-2-(phenoxymethyl)-1-propene (0.91 M, 3 ml) (Louw et. al. Tetrahedron, 48, 6087-6104, 1992, prepared from 2.74 mmol of 3-chloro-2-(phenoxymethyl)-1-propene) was slowly added to a solution of (2S)-1-tert-butoxycarbonyl-2-phenylpiperidin-3-one (Desc.1) in THF (3 ml). The solution was stirred at room temperature for 1 hour, quenched by addition of saturated ammonium chloride solution (20 ml) and extracted with ethyl acetate (20 ml). The organic phase was washed (saturated brine), dried (MgSO4), evaporated to a small volume and purified by chromatography on silica gel eluting with hexane containing increasing proportions of ethyl acetate between 0% to 20%. Evaporation of the fractions gave (2S,3R)-1-tert-butoxycarbonyl-3-hydroxy-3-(2-methylene-3-phenoxypropyl)-2-phenylpiperidine. MS (ES+) m/z 424 (M+H), 324 (M+2H-tBuOCO--), 368 (M+2H-tBu). 1H NMR (360 MHz, CDCl3) δ 7.48 (2H, d, J 6.9 Hz), 7.35-7.2 (6H, m) 6.9-6.88 (3H, m), 5.4 (1H, s), 5.15 (2H, d, J 13.7 Hz), 4.61 (2H, s), 4.11 (2H, m), 3.17 (1H, m), 2.66 and 2.59 (2H, AB d, J 14.0 Hz), 1.95 (2H, m), 1.79 (2H, m), 1.36 (9H, s).

Provenance & Evidence