Dimethylformamide → Ethyl 7-chloro-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

7-Chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, (U.S. Pat. No. 4,663,457) (20.0 g, 71 mmol) and dimethylformamide (0.5 mL) were added to dichloromethane (750 mL) to give a tan slurry. Oxalyl chloride (7.4 mL, 85 mmol) was added to this slurry over one minute and the reaction mixture stirred for 90 minutes, then an additional 2.0 mL of oxalyl chloride was added and stirring continued for 60 minutes. To the resulting brown solution was added absolute ethanol (4.3 mL, 78 mmol) and the mixture stirred for 4 hours and then cooled to 0° C. and stored overnight. The reaction was warmed to room temperature and an additional 2 mL of absolute ethanol was added and the stirring continued for 3 hours. The reaction was evaporated to a brown solid. The solid was heated in THF, filtered, and cooled to 0° C. The crystals formed were collected and dried to give the title compound (11.1 g, 50%).

Provenance & Evidence