1-Bromohexane → 4-Benzyl-2-(4-hexyloxy-phenyl)-morpholine

HRID 920544Notes

Reaction equation

HRID 920544 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].Br[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>O.O1CCOCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:15]=[CH:16][C:17]([O:20][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])=[CH:18][CH:19]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 81011-BromohexaneHCID 14797Potassium HydroxideHCID 669173494-(4-Benzyl-morpholin-2-yl)-phenol

Product 1

HCID 670328994-Benzyl-2-(4-hexyloxy-phenyl)-morpholineYield 75%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 4-(4-benzyl-morpholin-2-yl)-phenol (1.33 g; 4.94 mmol) in water (10 mL) and 1,4-dioxane (10 mL) was added KOH (0.55 g; 9.88 mmol), 1-bromohexane (1.04 mL; 7.41 mmol) and tetrabutylammonium bromide (0.16 g; 0.49 mmol), the resulting mixture was heated under reflux overnight. After cooling to RT the mixture was concentrated in vacuo, and partitioned between EtOAc and 5% aqueous NaHCO3solution. 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-benzyl-2-(4-hexyloxy-phenyl)-morpholine (1.31 g).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux overnight
  3. concentrationwas concentrated in vacuo
  4. custompartitioned between EtOAc and 5% aqueous NaHCO3solution
  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-16540e8b9a924589bae62f792c7b6010
Source dataset
uspto-grants-2016_03
Patent number
US09273017B2

Reaction notes

Loading…