Acetic Acid → 5-{[1-(2-fluoro-4-methoxyphenyl)-methylidene]amino}-1H-quinolin-2-one

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Reaction Steps

To 600 mg (3.9 mmol) 5-Amino-7-fluoro-1H-quinolin-2-one and 624 mg (3.9 mmol) 2-fluoro-4-methoxybenzaldehyde in 12 ml toluene are added 18 μl acetic acid and 2 g molecular sieve. The mixture is heated over 25 hours under reflux and filtrated through a path of cellites after cooling. The solvent is evaporated and the residue is two times azeotrophed with small portions of toluene to obtain 5-{[1-(2-fluoro-4-methoxyphenyl)-methylidene]amino}-1H-quinolin-2-one are quantitatively. 0.81 ml (11.6 mmol) 1,1,1-trifluoroepoxypropane in 12 ml THF and 3.5 ml hexane are cooled to −100° C. and 3.75 ml of a 2.5 M n-butyl lithium solution (9.4 mmol) in hexane are added over 10 minutes while the temperature does not exceed −95° C. 10 Minutes after complete addition 1.11 g (12 mmol) 5-{[1-(2-fluoro-4-methoxyphenyl)-methylidene]amino}-1H-quinolin-2-one in 10 ml THF are added over 15 minutes while the temperature does not exceed −95° C. After tree hours at −100° C. 3.75 ml diethyl ether are added and the reaction mixture is warmed to −10° C. over one hour. The reaction is quenched by addition of saturated ammonium chloride solution. The phases were separated and the aqueous layer is extracted twice with ethyl acetate, the combined organic phases washed with brine, dried over sodium sulphate and then evaporated. Flash chromatography on silica gel (acetone in hexane 0 to 80%) yields 410 mg of 5-{[(2-Fluoro-4-methoxyphenyl)(2-trifluoromethyl-oxiranyl)methyl]amino}-1H-quinolin-2-one.

Provenance & Evidence