Phenol → 29488-54-8

HRID 411604Notes

Reaction equation

HRID 411604 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[Cl:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.[OH-].[K+]>C(O)(C)C>[O:7]([CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:9].[O:7]([CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 996PhenolHCID 14797Potassium HydroxideHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)

Product 2

HCID 28409994-(2-phenoxyethyl)MorpholineHCID 6996069929488-54-8Yield 100.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-(2-Phenoxyethyl) morpholine was prepared by a modified method of Grail. et al (Journal of American Chemical Society, 1952, 74, 1313-1315). For example, 9.2 g of phenol and 18.6 g of N-(2-chloroethyl)morpholine HCl salt were dissolved in 120 ml of isopropanol and 12 g of potassium hydroxide was added with cooling. The reaction mixture was refluxed for 12 hours. Solid (KCl) was filtered off. The filtrate was distilled off. The residual material was treated with 150 ml of 1N NaOH, then, extracted with dichloromethane (200 ml). Dichloromethane layer was again washed with a solution of 0.1N sodium carbonate in 10% NaCl solution. Dichloromethane layer was dried over anhydrous magnesium chloride, and evaporated under reduced pressure. Residual syrup was dissolved in 100 ml of 1.5N HCl solution, and washed with 100 ml of chloroform. Aqueous layer was treated with 100 ml of toluene and water was removed by Dean-Stark apparatus by distillation. Residual toluene layer was cooled to give crystalline solid, which was collected by filtration. 12 g of N-[(2-phenoxy)ethyl]morpholine HCl salt (50% yield )was obtained.

Workup

  1. temperaturewith cooling
  2. temperatureThe reaction mixture was refluxed for 12 hours
  3. filtrationSolid (KCl) was filtered off
  4. distillationThe filtrate was distilled off
  5. additionThe residual material was treated with 150 ml of 1N NaOH
  6. extractionextracted with dichloromethane (200 ml)
  7. washDichloromethane layer was again washed with a solution of 0.1N sodium carbonate in 10% NaCl solution
  8. dry with materialDichloromethane layer was dried over anhydrous magnesium chloride
  9. customevaporated under reduced pressure
  10. dissolutionResidual syrup was dissolved in 100 ml of 1.5N HCl solution
  11. washwashed with 100 ml of chloroform
  12. additionAqueous layer was treated with 100 ml of toluene and water
  13. customwas removed by Dean-Stark apparatus by distillation
  14. temperatureResidual toluene layer was cooled
  15. customto give crystalline solid, which
  16. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-45e6ff9cead546d9947bc1fd7d146fc8
Source dataset
uspto-grants-2003_05
Patent number
US06559167B1

Reaction notes

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