Sodium hydride → (E)-3-[5-(4-Fluorophenyl)-1,2-dihydro-7-isopropyl-2-oxo1, 8-naphthyridin-6-yl]-prop-2-enal

Participants

Reaction Steps

A solution of 13.1 g (50 mmol) of diethyl 2-(cyclohexylamino)-vinyl-phosphonate in 80 ml of tetrahydrofuran is added dropwise at 0° C. under argon to a suspension of 3.0 g (100 mmol) of 80% strength sodium hydride in 80 ml of anhydrous tetrahydrofuran and the mixture is stirred at this temperature for 30 min. A solution of 13.0 g (42 mmol) of the compound from Example 4 in 80 ml of tetrahydrofuran is then added dropwise at 0° C.-5° C. and the mixture is then heated under reflux for 1 h. 200 ml of water are added cautiously and the mixture is extracted three times with ethyl acetate. After concentrating the organic phases, the residue is heated under reflux for 2 h with a mixture of 500 ml of toluene, 500 ml of water and 27.5 g (218 mmol) of oxalic acid dihydrate. The toluene phase is concentrated and the residue is treated with ethyl acetate. 11.35 g (80% of theory) of colorless crystals of m.p. 261° C. are obtained.

Provenance & Evidence