Sodium hydride → 5-Bromo-1-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-one

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Reaction Conditions

Reaction Steps

In a 2-L RBF, a mixture of 5-bromopyridin-2(1H)-one (30 g, 172 mmol) in DME (250 mL) and DMF (70 mL) was purged with nitrogen and cooled in an ice bath. NaH (60% dispersion, 8.0 g, 200 mmol) was added in small portions to the mixture (over 2 h), resulting in a yellow suspension. LiBr (35 g, 403 mmol) was added and the mixture was stirred at room temperature for 15 min before 4-(2-bromoethoxy)-7-methoxyquinoline (40.0 g, 142 mmol) was added. The mixture was then heated to 60° C. in an oil bath for 5 days. The mixture was cooled to room temperature. CH2Cl2 (300 mL) was added and the slurry was filtered through a pad of Celite. The filtrate was washed with NaOH (0.5 N, 3×150 mL), H2O (100 mL), and dried over Na2SO4. The solution was concentrated to give a soft sludge which was stirred with a mixture of hexane (150 mL)-THF (150 mL) at reflux. The mixture was let cooled to room temperature overnight. The soft cake was filtered and washed with 1:1 hexane-THF (100 mL) to afford the product as a white solid (35.5 g, 67%).

Provenance & Evidence