Acetic Acid → HCID 66932316, compound

Participants

Reaction Steps

A mixture of (E)-3-{4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (170 mg, 0.564 mmol, Intermediate 1, free base), AcOH (0.051 ml, 0.90 mmol), and HCHO (35% in H2O, 0.07 ml, 0.847 mmol) in MeOH (12 ml) and dioxane (3 ml) was stirred at RT for 20 min and then treated with 6-fluoro-1H-indole (100 mg, 0.734 mmol). The resulting solution was stirred at 50° C. for 1 h. The solvent was then evaporated, the residue dissolved with DCM and washed with 5% aqueous NaHCO3 and brine. The organic phase was dried over Na2SO4 and evaporated under vacuum. The crude mixture was purified by column chromatography (eluent: DCM/MeOH/NH4OH 97:3:0.3) to give (E)-3-{1′-(6-fluoro-1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester as a brown solid (140 mg).

Provenance & Evidence