Acetic Acid → 7-Fluoro-4-hydroxyquinoline-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 2.5 M n-butyl lithium in tetrahydrofuran (53.6 mL, 134 mmol) in 54 mL of tetrahydrofuran at −78° C. is added dropwise a solution of acetonitrile (7.1 mL, 136 mmol) in 100 mL of tetrahydrofuran. After stirring at −78° C. for 10 min, a solution of ethyl 2-{[(1E)-(dimethylamino)methylidene]amino}-4-fluorobenzoate (14.5 g, 60.9 mmol) in 100 mL of tetrahydrofuran is added over a period of 1.5 h. After stirring at −78° C. for 2 h, the reaction temperature is slowly allowed to warm to −10° C. The mixture is then cooled to −78° C. and acetic acid (18.3 g, 305 mmol) is added dropwise. The reaction mixture is allowed to warm to room temperature and stirred for 3 days. The precipitate is collected by filtration washing with tetrahydrofuran, water, diethyl ether, ethyl acetate and then additional diethyl ether to give 7.95 g of 7-fluoro-4-hydroxyquinoline-3-carbonitrile as an off-white solid, mp>250° C.

Provenance & Evidence