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

HRID 1594845Notes

Reaction equation

HRID 1594845 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].CCN(CC)CC.Br[CH2:17][CH2:18][CH2:19][CH2:20][C:21](Cl)=[O:22].C(=O)([O-])[O-].[Cs+].[Cs+].[OH-].[Na+].Cl>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl.CN(C=O)C.C1COCC1.O>[O:22]=[C:21]1[CH2:20][CH2:19][CH2:18][CH2:17][N:1]1[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8]

Participants

12

Reactant 6

HCID 313Hydrochloric AcidHCID 58012-AminophenolHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 5211735-Bromovaleryl chloride

Product 1

HCID 115066091-(2-Hydroxyphenyl)piperidin-2-one

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-838a87628ab34d1cae281d4fdf7e0b4b
Source dataset
uspto-grants-2001_09
Patent number
US06284755B1

Reaction notes

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