反应详情

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.

1. washthe reaction mixture was washed with 1N HCl until the aqueous layer
2. washwashed with H2O, aqueous saturated NaHCO3 solution, brine
3. dry with materialdried (Na2SO4)
4. filtrationFiltration and concentration to dryness
5. customgave a yellow oil which
6. custompartitioned between EtOAc and ice water
7. extractionThe aqueous layer was extracted with EtOAc (3×)
8. washwashed with H2O, aqueous saturated NaHCO3 solution, brine
9. dry with materialdried (Na2SO4)
10. filtrationFiltration and concentration to dryness
11. customgave a crude product which
12. stirringwith stirring at ambient temperature for 2 hr
13. concentrationconcentrated
14. extractionextracted with EtOAc (3×)
15. washwashed with H2O, aqueous saturated NaHCO3 solution, brine
16. dry with materialdried (Na2SO4)
17. filtrationFiltration and concentration to dryness