O-Methylhydroxylamine → Ethyl 1,4-dihydro-1-methoxy-4-oxo-3-quinolinecarboxylate

Participants

Reaction Steps

Ethyl 3-ethoxy-2-(2-fluorobenzoyl)-2-propenoate (4.0 g, prepared from ethyl 3-(2-fluorophenyl)-3-oxopropanoate as in Preparation No. 59) and O-methylhydroxylamine (16 mmol, prepared by mixing 1 eq of sodium ethoxide with 1 eq of O-methylhydroxylamine hydrochloride in ethanol) are stirred in ethanol (20 mL) for 1 hour at rt. The mixture is concentrated, diluted with dioxane (75 mL) and re-concentrated to remove any remaining ethanol. The resulting enamine is diluted in dioxane (70 mL) and sodium hydride (60% dispersion, 0.64 g) is added. The mixture is heated to reflux for 2.5 hours, cooled to rt and concentrated in vacuo. The remaining residue is partially dissolved in ethanol (100 mL) and filtered. The filtrate is concentrated in vacuo and chromatographed (7% MeOH/CH2Cl2). The combined fractions are concentrated, leaving a residue which is recrystallized in a 1:1 ether/hexanes mixture to afford 0.95 g of ethyl 1-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate (Mp 120-121° C.) as a white solid.

Provenance & Evidence