Sodium hydride → 7-[2-Cyclopropyl-4-(4-fluorophenyl) quinolin-3-yl]-7-hydroxy-3,5-dioxoheptanoic acid ethyl ester

Participants

Reaction Steps

In a mixture solution of 2.40 g of an oily 60% sodium hydride and 200 ml of tetrahydrofuran, a mixture solution of 10.3 g of 3,5-dioxohexanoic acid ethyl ester and 40 ml of tetrahydrofuran was dropped in 20 minutes while keeping an inner temperature at 2° C. or less. After allowing a reaction for 50 minutes at −10° C., 75 ml of a hexane solution of 1.6 M n-butyl lithium was dropped in 40 minutes with the inner temperature kept at −20 to −15° C., while allowing a reaction for 40 minutes at an inner temperature of 2° C. or less. In this case, furthermore, while keeping an inner temperature of −15° C. or less, a mixture of 11.7 g of 2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-carbaldehyde and 80 ml of tetrahydrofuran was dropped in 40 minutes and was then reacted at 10° C. or less for 1 hour. Furthermore, while keeping an inner temperature of 5° C. or less, 14.4 ml of acetic acid and 40 ml of toluene were added in a reaction system, followed by washing with 100 ml of water and 100 ml of saturated brine in that order. After the solvent is distilled off, the residue thus obtained was added with 100 ml of hexane and 5 ml of ethyl acetate so as to be crystallized, followed by filtrating and drying it to obtain 16.6 g (yield: 89%) of 7-[2-cyclopropyl-4-(4-fluorophenyl) quinolin-3-yl]-7-hydroxy-3,5-dioxoheptanoic acid ethyl ester was obtained.

Provenance & Evidence