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

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

A solution of 3-bromopyridine (9.09 mL, 94.31 mmol) in diethyl ether (50 mL) was added dropwise to a stirred solution of 1.6M n-butyl lithium in hexane (58.9 mL, 94.31 mmol) in diethyl ether (500 mL) cooled to −78° C., over a period of 15 minutes under nitrogen. The resulting suspension was stirred at −78° C. for 1 hour. A solution of benzyl 4-oxopiperidine-1-carboxylate (20 g, 85.74 mmol) in diethyl ether (50 mL) and THF (50 mL) was added dropwise over 15 minutes. The reaction mixture was stirred at −78° C. for 1 hour, warmed to 0° C. over 2.5 hours and quenched with saturated ammonium chloride solution (500 ml). The mixture was extracted with ethyl acetate (2×500 mL) and the combined extracts were washed with brine (200 mL) then dried over MgSO4 and filtered through a short pad of silica. The silica pad was washed through with ethyl acetate (4×250 mL) and the filtrate was concentrated under vacuum. The residue was purified by flash silica chromatography eluting with ethyl acetate. Pure fractions were evaporated to dryness to afford benzyl 4-hydroxy-4-(pyridin-3-yl)piperidine-1-carboxylate (12.8 g, 48%) as an oil.

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