Pyridine → Benzyl 4-hydroxy-4-(pyridin-3-yl)piperidine-1-carboxylate

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Reaction Steps

To a cooled solution (-78° C.) of n-butyllithium (2.0M in hexane, 12.9 mL, 28.3 mmol, 1.2 eq) in tetrahydrofuran (200 mL) under nitrogen was added 3-bromopyridine (2.27 mL, 23.6 mmol, 1.1 eq). The solution became a dark green color as the pyridine was added. The reaction was stirred at this temperature for 1h, at which time 1-carbobenzyloxy-4-piperidone (described in example 87c) (5.00 g, 21.4 mmol) was added as a tetrahydrofuran solution (20 mL). The cooling bath was removed and the reaction warmed to room temperature, stirring at that temperature for 18 h. The reaction was quenched by the addition of water (125 mL) and the aqueous phase extracted with ethyl acetate (3×75 mL). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and reduced to an oil. The reaction product was purified by flash chromatography over silica gel (300 mL, eluent: ethyl acetate) to yield 5.00 g (75%) of the title compound as an oil. TLC analysis (Rf 0.10, ethyl acetate). MS (CI, CH4) m/z 313 (M+1,100), 341 (M+29,15), 295 (15).

Provenance & Evidence