Sodium Hydroxide → HCID 66932561, compound

Participants

Reaction Steps

4 M NaOH (0.148 ml, 0.591 mmol) was added to a solution of (E)-3-{1′-ethylcarbamoyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (220 mg, 0.591 mmol) in dioxane (3 ml) and water (3 ml) and the mixture was stirred at RT for 1 h. Further 4 M NaOH (0.073 ml) was added and the mixture was stirred for additional 2 h. Dioxane was removed under vacuum and the residue was acidified with 2 M HCl. The resulting precipitate was filtered to give (E)-3-{1′-ethylcarbamoyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid. The crude compound (163 mg) was dissolved in a mixture of DCM (3 ml) and TEA (0.126 ml, 0.91 mmol). EDC (174 mg, 0.91 mmol) and HOBT (61 mg, 0.45 mmol) were added at 0° C. and the resulting solution was stirred at RT for 1 h. NH2OTHP (66 mg, 0.56 mmol) was added and the mixture was stirred at RT for 4 h and then washed with 5% aqueous solution of NaHCO3. The organic phase was washed with water, dried over Na2SO4 and evaporated. The crude residue was purified by column chromatography (eluent: DCM/MeOH/NH4OH 97:3:0.3) and the resulting (E)-3-{1′-ethylcarbamoyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide was dissolved in DCM and treated with 4 M HCl in dioxane for 2 h. The precipitate was filtered and washed with DCM to give the title compound as a pale yellow powder (118 mg).

Provenance & Evidence