3-Bromopyridine → Ethyl 6-hydroxy-6-(3-pyridinyl)-3-azabicyclo[3.2.1]octane-3-carboxylate

To a solution of 3-bromopyridine (1.04 g, 6.58 mmol) in dry diethyl ether (20 ml) at −78° C. was added 2.5 M n-butyllithium (2.63 ml, 6.6 mmol). The reaction was stirred for 30 min under nitrogen. The pyridinyllithium solution was then slowly transferred by cannula into a solution of ethyl 6-oxo-3-azabicyclo[3.2.1]octane-3-carboxylate (1.00 g, 5.07 mmol) in THF (10 ml) at −78° C. The reaction was stirred 4 h at −78° C. and then quenched with saturated aqueous ammonium chloride (10 ml). The reaction was then extracted with chloroform (3×25 ml), the combined extracts dried over sodium sulfate, filtered, and concentrated by rotary evaporation. Excess pyridine was removed by repeated azeotropic rotary evaporation with toluene to yield the desired product (1.20 g, 86%).

1. stirringThe reaction was stirred 4 h at −78° C.
2. customquenched with saturated aqueous ammonium chloride (10 ml)
3. extractionThe reaction was then extracted with chloroform (3×25 ml)
4. dry with materialthe combined extracts dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated by rotary evaporation
7. customExcess pyridine was removed
8. customrotary evaporation with toluene

ORD record

ord-7b3e7cfaa2614f1a8e66be11f642cdb4

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07402592B2