Benzyl 4-hydroxy-4-(pyridin-2-yl)piperidine-1-carboxylate synthesis

Yield:161610-16-8 27%

Reaction Conditions:

with n-butyllithium;NH₄Cl in tetrahydrofuran;

Steps:

36.A benzyl 4-hydroxy-4-(2-pyridinyl)-1-piperidinecarboxylate

EXAMPLE 36A benzyl 4-hydroxy-4-(2-pyridinyl)-1-piperidinecarboxylate 2-Bromopyridine (0.470 mL, 5 mmol) in THF (20 mL) was treated with n-BuLi 1.6 M in hexanes (5.2 ml, 5.2 mmol) dropwise at -60° C. After stirring at -60° C. for 30 minutes, the reaction mixture and treated with benzyl 4-oxo-1-piperidinecarboxylate (1.14 g, 4.9 mmol) in THF (10 mL) slowly. After stirring an additional 15 minutes at -60° C., the reaction mixture was quenched with a saturated aqueous solution of NH₄Cl, allowed to warm to room temperature and was extracted into dichloromethane. The organics were combined, dried on MgSO₄, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (elution with hexanes:ethyl acetate, 1:1) to provide the title compound (400 mg, 27% yield). ¹H NMR (300 MHz, DMSO-d₆) δ1.54 (m, 2H), 2.05 (m, 2H), 3.25 (m, 2H), 3.95 (m, 2H), 5.11 (s, 2H), 5.35 (s, 1H), 7.25 (m, 1H), 7.35 (m, 5H), 7.68 (m, 1H), 7.79 (m, 1H), 8.5 (m, 1H); MS (DCI/NH₃) m/e 313 (M+H)⁺.

References:

US2004/29887,2004,A1