Monobenzone → 4-(2-Azepan-1-yl-ethoxy)-phenol

HRID 1513868Notes

Reaction equation

HRID 1513868 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[C:4]1C=CC=CC=1.Cl.[N:19](=[CH:27][CH2:28]Cl)[CH2:20][CH2:21][CH2:22][CH2:23]CCCl.C([O-])=O.[NH4+]>C(OCC)(=O)C.CO.[Pd].O.CN(C=O)C>[N:19]1([CH2:4][CH2:3][O:10][C:11]2[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=2)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:28][CH2:27]1

Participants

10

Reactant 4

HCID 7638MonobenzoneHCID 24758Sodium hydrideHCID 2723923Ammonium formate2×HCID 534452772-(hexamethyleneimino)ethyl chloride HCl

Product 1

HCID 670048004-(2-Azepan-1-yl-ethoxy)-phenolYield 59,879.301%

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

Add sodium hydride (18 g, 0.45 mol) into a solution of 4-benzyloxylphenol (41 g, 0.20 mol) and 2-(hexamethyleneimino)ethyl chloride hydrochloride (44 g, 0.22 mmol) in TIE (600 mL) and DMF (100 mL) at room temperature. Heat to 60° C. for 30 minutes. Pour the solution into ice and water. Dilute with ethyl acetate (500 mL) and separate layers. Dry the organic layer with magnesium sulfate, filter and concentrate under reduced pressure to give brown oil. Dissolve the oil in ethyl acetate (500 mL) and methanol (500 mL). Add ammonium formate (100 g, 1.59 mol) and palladium on carbon (10 g, 9.4 mmol). Heat the mixture to reflux for 30 minutes. Add ammonium formate (100 g, 1.59 mol) and palladium on carbon (10 g, 9.4 mmol). Heat the reaction mixture for 30 minutes. Filter the suspension through a pad of celite and elute with ethyl acetate (500 mL). Evaporate solvent under reduced pressure and add water (100 mL). Dilute the mixture with ethyl acetate (500 mL) and separate layers. Wash the organic layer with saturated sodium bicarbonate solution (2×200 mL), dry with magnesium sulfate, filter and evaporate solvent under reduced pressure to give 31 g (64%) of 4-(2-azepan-1-yl-ethoxy)-phenol.

Workup

  1. customseparate layers
  2. dry with materialDry the organic layer with magnesium sulfate
  3. filtrationfilter
  4. concentrationconcentrate under reduced pressure
  5. customto give brown oil
  6. temperatureHeat the mixture
  7. temperatureto reflux for 30 minutes
  8. temperatureHeat the reaction mixture for 30 minutes
  9. filtrationFilter the suspension through a pad of celite
  10. washelute with ethyl acetate (500 mL)
  11. additionEvaporate solvent under reduced pressure and add water (100 mL)
  12. additionDilute the mixture with ethyl acetate (500 mL)
  13. customseparate layers
  14. washWash the organic layer with saturated sodium bicarbonate solution (2×200 mL)
  15. dry with materialdry with magnesium sulfate
  16. filtrationfilter
  17. customevaporate solvent under reduced pressure

Sources & evidence

ORD record
ord-a9a41b106e6840b985c606ab53976c9f
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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