Acetic Acid → HCID 66932387, 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 (0.039 ml, 0.67 mmol), and HCHO (35% in H2O, 0.055 ml, 0.67 mmol) in MeOH (8 ml) and dioxane (2 ml) was stirred at RT for 20 min and then treated with indole (94 mg, 0.80 mmol). The resulting solution was stirred at RT overnight and then further HCHO (0.02 ml) was added. After heating at 50° C. for 4 h, the solvent was evaporated and the residue was dissolved with DCM and washed with 5% aqueous NaHCO3 and brine. The organic phase was dried over Na2SO4, evaporated and the crude product was purified by column chromatography (eluent: DCM/MeOH/NH4OH 96:4:0.4) to give (E)-3-{1′-(1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester as a white solid (140 mg).

Provenance & Evidence