Hydrochloric Acid → HCID 66932348, compound

Participants

Reaction Steps

4 M NaOH (0.081 ml, 0.325 mmol) was added to a solution of (E)-3-{1′-(1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (140 mg, 0.325 mmol) in dioxane (2 ml) and water (1 ml) and the mixture was stirred at RT for 10 h. The pH was brought to 4 with 2 M HCl and the solvent was removed under vacuum to give (E)-3-{1′-(1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid. The crude compound (135 mg) was dissolved in THF (12 ml). TEA (0.092 ml, 0.66 mmol), EDC (126 mg, 0.66 mmol) HOBT (44 mg, 0.33 mmol) and NH2OTHP (48 mg, 0.41 mmol) were added and the mixture was stirred at RT overnight. The solvent was removed and the residue was partitioned between DCM and water. 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). The resulting (E)-3-{1′-(1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide was dissolved in DCM and treated with HCl/Et2O for 3 h. The precipitate was filtered and washed with DCM to give (E)-3-{1′-(1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-hydroxy-acrylamide hydrochloride as a white solid (40 mg).

Provenance & Evidence