1,2-Dichloroethane → HCID 87258296, compound

Participants

Reaction Steps

(±)-(E)-3-[1′-Acetyl-4-oxo-spiro(chromane-2,3′-piperidine)-6-yl]-acrylic acid (crude compound from STEP B, 590 mg) was dissolved in DCM (30 ml) and TEA (0.498 ml, 3.59 mmol). EDC (513 mg, 2.68 mmol) and HOBt (362 mg, 2.68 mmol) were added and the mixture was stirred for 10 min at RT. NH2OTHP (251 mg, 2.15 mmol) was added and the solution was stirred overnight at RT and was then partitioned between 5% NaHCO3 and DCM. The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness. The crude mixture was purified by column chromatography (eluent: DCM/MeOH 99:1 to 97:3) to give (±)-(E)-3-[1′-acetyl-4-oxo-spiro(chromane-2,3′-piperidine)-6-yl]-N-(tetrahydro-pyran-2-yloxy)-acrylamide that was dissolved in DCM and treated with 4 M HCl in dioxane for 3 h. The precipitate was collected by filtration and washed with DCM to give (±)-(E)-3-[1′-acetyl-4-oxo-spiro(chromane-2,3′-piperidine)-6-yl]-N-hydroxy-acrylamide as pale yellow powder (404 mg).

Provenance & Evidence