Silane, trimethyl(2-propyn-1-yloxy)- → (2S,3R)-1-tert-Butoxycarbonyl-3-(3-hydroxypropyn-1-yl)-2-phenylpiperidin-3-ol

Participants

Reaction Conditions

Reaction Steps

To a cooled (−5° C.) solution of ethylmagnesium bromide (1M in tetrahydrofuran, 130 ml, 130 mmol) in tetrahydrofuran was added O-trimethylsilylpropargyl alcohol slowly. The reaction was stirred at 0° C. for 20 minutes and then at room temperature for 2 hours, before cooling to −10° C. To this was then added a solution of (2S)-1-tert-butyloxycarbonyl-2-phenylpiperidin-3-one (Desc. 1; 30 g, 108 mmol) in tetrahydrofuran keeping the temperature below 5° C. The reaction was stirred at room temperature overnight, quenched by addition of water/saturated aqueous ammonium chloride (200 ml/200 ml) and extracted with ethyl acetate (2×200 ml). The combined organic phases were dried (MgSO4) and evaporated to an oil. This oil was dissolved in ethyl acetate (400 ml) and a solution of tetrabutylammonium fluoride (1M in tetrahydrofuran, 130 ml, 130 mmol) added. After stirring at room temperature for 2 hours, water (200 ml) was added, and the two layers separated. The aqueous phase was further extracted with ethyl acetate (200 ml), the organic layers dried (MgSO4) and evaporated to give the product as an oil (50 g) which was used crude for Description 3. 1H NMR (CDCl3) δ7.53-7.55 (2H, m), 7.19-7.35 (3H, m) 5.56 (1H, s), 4.27 (2H, s), 3.99-4.03 (1H, m) 3.25 (1H, bs), 2.77-2.81 (1H, m) 2.77 (1H, bs), 2.12-2.20 (1H, m) 1.91-1.99 (2H, m), 1.77-1.83 (1H, m), 1.39 (9H, s).

Provenance & Evidence