Diethyl Ether → Ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate

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Reaction Steps

A solution of ethyl 3-(dimethylamino)-2-(2,4,5-trifluorobenzoyl)acrylate (Example 48a) (75 g, 249 mmol) in a mixture of Ethanol (100 mL)/Diethyl ether (200 mL) was added to cyclopropanamine (34.5 mL, 498 mmol). After 2 h of stirring at rt, LCMS showed complete disappearance of starting material. The reaction mixture was evaporated under reduced pressure, the oily residue was dissolved in N,N-Dimethylformamide (DMF) (250 mL) and potassium carbonate (103 g, 747 mmol) was then added. The reaction mixture was stirred at 100° C. for 2 h, and LCMS showed completion of reaction. Cold water was added to the mixture. The precipitates were collected by filtration and dried to afford ethyl 1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (71 g, 242 mmol, 97% yield) as a pale yellow solid. LCMS: [M+H]+: 294.1.

Provenance & Evidence