3-Bromo-5-(propan-2-yloxy)pyridine → Ethyl 6-hydroxy-6-(5-isopropoxy-3-pyridinyl)-3-azabicyclo[3.2.1]octane-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-bromo-5-isopropoxypyridine (0.66 g, 3.1 mmol) in dry diethyl ether (15 mL) at −78° C. was added 2.5 M n-butyllithium (1.2 mL, 3.0 mmol). The reaction was stirred for 30 min under nitrogen at −78° C. and then slowly transferred by cannula into a solution of ethyl 6-oxo-3-azabicyclo[3.2.1]octane-3-carboxylate (0.30 g, 1.5 mmol) in THF (15 mL) at −78° C. The reaction was stirred 4 h at −78° C. and then warmed to ambient temperature overnight, at which time it was quenched with saturated aqueous ammonium chloride (20 mL). The reaction was then extracted with chloroform (2×10 mL), and the combined extracts were dried over sodium sulfate, filtered, and concentrated by rotary evaporation. Excess pyridine was removed by repeated azeotropic rotary evaporation with toluene, and the residue was chromatographed on a silica gel column (with 5% methanol in chloroform) to yield the desired product (0.34 g, 61%).

Provenance & Evidence