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

Temperature

-78 °C

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%).

1. stirringThe reaction was stirred 4 h at −78° C.
2. temperaturewarmed to ambient temperature overnight, at which time it
3. customwas quenched with saturated aqueous ammonium chloride (20 mL)
4. extractionThe reaction was then extracted with chloroform (2×10 mL)
5. dry with materialthe combined extracts were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated by rotary evaporation
8. customExcess pyridine was removed
9. customrotary evaporation with toluene
10. customthe residue was chromatographed on a silica gel column (with 5% methanol in chloroform)

ORD record

ord-80ec891f246646dd92d3e03023b9617e

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07897611B2