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

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Reaction Steps

To a suspension of sodium hydride (100 mg, 4.17 mmol) in tetrahydrofurane (4 ml) under argon is added at −5° C. ethyl acetoacetate (546 mg, 4.19 mmol), butyllithium (n-heptane solution (soln.), 1.55 ml, 4.19 mmol), and a solution of 3-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-N-methoxy-N-methyl-acrylamide in tetrahydrofurane (9 ml). After 5 h stirring at room temperature, the reaction mixture is added to a suspension of sodium hydride (200 mg, 8.33 mmol), ethyl acetoacetate (1.09 g, 8.39 mmol), and butyllithium (n-heptane soln., 3.1 ml, 8.37 mmol) in tetrahydrofurane (8 ml) at −5 to 0° C. After 60 minutes at 0° C., acetic acid (100%, 2.25 g, 37.5 mmol), 25% aq. NaCl (5 ml), and water (3 ml) are added and the mixture is stirred vigorously for 10 min. The (upper) organic phase is successively washed with 25% aq. NaCl (5 ml) and water (5 ml), and evaporated to dryness under reduced pressure. The residue is dried under vacuum at 40° C. and purified by silica gel chromatography (hexane/ethyl acetate 3:1) to give (E)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3,5-dioxo-hept-6-enoic acid ethyl ester, semisolid honey. MS (ES): [M+H]+ 446.

Provenance & Evidence