2-Bromopyridine → 3-(2-Pyridyl)cyclopentan-1-one

Participants

Reaction Steps

A solution of thiophene (0.50 g, 6.0 mmol), diethyl ether (50 mL), and n-BuLi (2.5 M, 2.20 mL, 5.50 mmol) was stirred at room temperature for 1 hour. The reaction mixture was cooled to <5° C. and copper iodide (1.05 g, 5.50 mmol) was added. The reaction mixture was warmed to room temperature and stirred for 1 hour. In a separate flask, a solution of 2-bromopyridine (0.87 g, 5.50 mmol) in diethyl ether (50 mL) was cooled to <−70° C. and n-BuLi (2.5 M, 2.20 mL, 5.50 mmol) was added. The reaction mixture was warmed to room temperature and stirred for 10 minutes. The 2-lithiopyridine reagent was added to the first reaction mixture via cannula and stirred at room temperature for 1 hour. To the reaction mixture was added 2-cyclopenten-1-one (0.45 g, 5.50 mmol) in diethyl ether (10 mL) and the reaction mixture was stirred for 1 hour. The reaction was poured into EtOAc (150 mL) and washed with brine (100 mL), dried (Na2SO4), filtered, and concentrated. The material was purified by flash column chromatography (20% EtOAc/hexanes), to provide the title compound (0.38 g, 43%). 1H NMR (CD3OD, 300 MHz) δ 2.10-2.19 (m, 1H), 2.13-2.66 (m, 5H), 3.56-3.68 (m, 1H), 7.27 (ddd, J=1.0, 5.1, 7.5 Hz, 1H), 7.38 (dd, J=1.02, 7.80 Hz, 1H), 7.76 (ddd, J=2.0, 7.80, 7.80 Hz, 1H), 8.47-8.50 (m, 1H); MS (DCI) m/z 162 (M+H)+.

Provenance & Evidence