Hydrochloric Acid → 1-(2-Hydroxyphenyl)piperidin-2-one

Participants

Reaction Steps

To a solution of 2-aminophenol (1.09 g, 0.01 mol), Et3N (4.46 mL, 0.032 mol) and 4-dimethylaminopyridine (0.122 g, 0.001 mol) in CHCl3 (20 mL) in an ice-H2O bath was added dropwise 5-bromovaleryl chloride (2.95 mL, 0.022 mol) with stirring. After 2 hr, the reaction mixture was washed with 1N HCl until the aqueous layer was acidic, then washed with H2O, aqueous saturated NaHCO3 solution, brine, and dried (Na2SO4). Filtration and concentration to dryness gave a yellow oil which solidifed on standing. This bisacylated product was dissolved in DMF (20 mL) and heated at 80° C. with cesium carbonate (4.89 g, 0.015 mol) for 3 hr, then partitioned between EtOAc and ice water. The aqueous layer was extracted with EtOAc (3×), the organics combined, washed with H2O, aqueous saturated NaHCO3 solution, brine, and dried (Na2SO4). Filtration and concentration to dryness gave a crude product which was treated with 1N NaOH solution (12 mL, 0.012 mol) in THF (20 mL)—H2O (10 mL) with stirring at ambient temperature for 2 hr. The reaction mixture was neutralized with 1N HCl (12 mL, 0.012 mol), concentrated, and extracted with EtOAc (3×), the organics combined, washed with H2O, aqueous saturated NaHCO3 solution, brine, and dried (Na2SO4). Filtration and concentration to dryness gave the title compound.

Provenance & Evidence