Cyclopropylamine → 1-Cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid Ethyl Ester

Participants

Reaction Conditions

Reaction Steps

A 12 L stirred flask was charged with 4.8 L of tetrahydrofuran, 1584 g of ethyl 2,3,4,5-tetrafluorobenzoylacetate and 834 ml of dimethylformamide dimethyl acetal. After establishing a nitrogen atmosphere, this mixture was heated to reflux for 1 hour and then stirred at ambient temperature for four hours. The mixture was cooled and maintained at 4°-5° C. while adding 438 ml of cyclopropylamine over a period of 35 minutes. It was then stirred at 3°-5° C. for 1 hour and concentrated in vacuo. The yellow crystalline solid was dissolved in 3.6 L of dimethylformamide and 912 g of powdered potassium carbonate was added with strong stirring. The slurry was then heated on a steam bath for 1 hour (maximum internal temperature was 108° C. for 5 minutes). The hot mixture was poured into 30 L of cold water. Filtration, washing first with 6 L of cold water and then 6 L of cold ethanol followed by drying in vacuo at 50° C. gave 1615 g of product (86.5% yield).

Provenance & Evidence