Sulfuric Acid → Ethyl 3-(2-chloro-6,7-difluoro-3-quinolyl)-3-oxopropionate

Participants

Reaction Conditions

Reaction Steps

A suspension of 2-chloro-6,7-difluoroquinoline-3-carboxylic acid (14.13 g) in thionyl chloride (29 cc) and trichloromethane (220 cc) is heated to a temperature in the region of 60° C. for 4 hours. The solution obtained is concentrated to dryness under reduced pressure (20 kPa) at approximately 60° C. The residue obtained is taken up with n-hexene (75 cc), drained and washed with the same solvent (2×60 cc). The yellow solid obtained (14.4 g) is dissolved in tetrahydrofuran (115 cc). This solution is introduced dropwise, with stirring, in the course of 35 minutes at between 5° and 10° C. into a solution (70 cc) of magnesium chelate of ethyl monomalonate in tetrahydrofuran, prepared under the conditions described below. The temperature is allowed to rise to approximately 20 C. and the mixture is stirred for a further 2 hours under these conditions. The solution obtained is introduced dropwise, with stirring, in the course of 30 minutes and at a temperature in the region of 5° C. into 0.5 N sulphuric acid (560 cc). The temperature of the suspension obtained is allowed to rise to 20° C. and the mixture is stirred for a further 1 hour and a half at this temperature. The product is extracted with ethyl acetate (3×250 cc). The combined organic extracts are washed with water (2×250 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 kPa) at 50° C. The residue obtained is taken up with n-hexane (50 cc) containing isopropyl ether (20%), drained, washed with the same mixture (10 cc) and recrystallized in isopropanol (60 cc) containing n-hexane (30%). Ethyl 3-(2-chloro-6,7-difluoro-3-quinolyl)-3-oxo-propionate (11.84 g) is obtained in the form of a cream-colored solid, m.p. 107° C.

Provenance & Evidence