Sodium hydride → Cis(+/-)1-{2-[4-(dibenzylamino)-3-methoxypiperidin-1-yl]ethyl}-5,7-difluoroquinolin-2(1H)-one

Participants

Reaction Steps

A solution of 5,7-difluoroquinolin-2(1H)-one (Intermediate 25, 300 mg, 1.70 mmol) in dry DMF (10 mL) was treated with sodium hydride (60% in oil, 80 mg, 2.00 mmol) with cooling in an ice bath. The reaction was stirred at room temperature for 90 min. The reaction was again cooled in an ice bath and treated with a solution of cis(±)2-[4-(dibenzylamino)-3-methoxypiperidin-1-yl]ethyl methanesulfonate in dry DMF (10 mL) (Intermediate 169, 1.2 eq, 2.00 mmol). The reaction was stirred at room temperature overnight. It was quenched with a small amount of water and concentrated to dryness. Residual DMF was removed by co-evaporating with toluene and the residue was partitioned between ethyl acetate (50 mL) and water (20 mL). The biphasic mixture was filtered, the phases separated and the aqueous phase was back extracted two times with ethyl acetate (2×50 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to dryness. Chromatography on silica gel with a gradient of 10-20% acetone in hexanes gave 240 mg (27%) of product as a colorless solid.

Provenance & Evidence