Acetic Acid → (E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid diethyl amide

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Reaction Conditions

Reaction Steps

To a suspension of sodium hydride (600 mg, 25.0 mmol) in tetrahydrofurane (20 ml) under argon is added at −5° C. diethyl acetoacetamide (3.93 g, 25.0 mmol) in tetrahydrofurane (2.0 ml), tetrahydrofurane (22.0 ml), butyllithium (n-heptane solution, 9.2 ml, 25.0 mmol), and a solution of 3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-N-methoxy-N-methyl-acrylamide (4.51 g, 12.0 mmol) in tetrahydrofurane (40 ml). After 1 h stirring at −5 to 0° C., acetic acid (4.4 g, 73.3 mmol), 25% aq. NaCl (10 ml), and water (10 ml) are added to the reaction mixture and the mixture is stirred vigorously for 10 min. The (upper) organic phase is washed with 25% aq. NaCl (2×20 ml), the water phases are extracted with ethylacetate (25 ml) and the combined organic phases filtered and evaporated to dryness under reduced pressure. The residue is purified by silica gel chromatography (hexane/ethyl acetate 1:1) to give (E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid diethyl amide. Mp. 97-105° C., MS (ES): [M+H]+ 473.

Provenance & Evidence