Potassium Hydroxide → 4-(4-Benzyl-morpholin-2-yl)-phenol

HRID 2167855Notes

Reaction equation

HRID 2167855 reaction equation
[CH2:1]([N:8]1[CH2:13][CH:12]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:21].[K+]>O.O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>[CH2:1]([N:8]1[CH2:9][CH2:10][O:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([OH:21])=[CH:16][CH:15]=2)[CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 2

HCID 14797Potassium HydroxideHCID 580978794-Benzyl-2-(4-bromo-phenyl)-morpholine

Product 1

HCID 669173494-(4-Benzyl-morpholin-2-yl)-phenolYield 52%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 4-benzyl-6-(4-bromo-phenyl)-morpholine (8.70 g; 26.19 mmol) in water (25 mL) and 1,4-dioxane (25 mL) was added KOH (3.23 g; 57.61 mmol), tris(dibenzylideneaceton)dipalladium(0) (479.6 mg; 0.52 mmol) and di-tert-butyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (444.8 mg; 1.05 mmol). The resulting mixture was heated under reflux for two hours. After cooling to RT the reaction mixture was concentrated in vacuo. The residue was partitioned between EtOAc and 5% aqueous NaHCO3 solution. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, Et2O:hexanes 1:1) to afford 4-(4-benzyl-morpholin-2-yl)-phenol (3.67 g).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux for two hours
  3. concentrationwas concentrated in vacuo
  4. customThe residue was partitioned between EtOAc and 5% aqueous NaHCO3 solution
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (SiO2, Et2O:hexanes 1:1)

Sources & evidence

ORD record
ord-d6b7c333570144d0aaa8357b31bdf646
Source dataset
uspto-grants-2015_06
Patent number
US09045441B2

Reaction notes

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