Trimethylsilylacetylene → 1,1-Dimethylethyl 4-hydroxy-4-[(trimethylsilyl)ethynyl]-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a cooled (-40° C.) solution of trimethylsilylacetylene (34 ml 241 mmol) in anhydrous tetrahydrofuran (400 ml) under an atmosphere of nitrogen was added slowly n-butyl lithium (96 ml of a 2.5. M solution in hexanes, 241 mmol). After addition the mixture was stirred at -40° C. for 1 hour then cooled to -78° C. To this mixture was added via a cannula a solution of 1-tert-butyloxycarbonyl-4-piperidone (40 g, 201 mmol) in anhydrous tetrahydrofuran (250 ml). After addition the mixture was stirred at -78° C. for 1 hour, the cooling bath removed and the mixture stirred at room temperature for 72 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride (300 ml), stirred for a further 10 minutes and poured into water (500 ml) and extracted with ethyl acetate (3×300 ml). The combined organic solutions were washed with water (500 ml), brine (300 ml), dried (MgSO4) and evaporated to afford the title compound (55 g, 92%); mp 75° C.; δH (250 MHz, CDCl3) 0.19 (9H, s), 1.48 (9H, s), 1.63-1.74 (2H, m), 1.80-1.92 (2H, m), 3.18-3.28 (2H, m), 3.71-3.84 (2H, m); mlz (ES) 298 (M+ +1).

Provenance & Evidence