Cesium carbonate → HCID 66653950, compound

HRID 588231Notes

Reaction equation

HRID 588231 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[OH:9].[H-].[Na+].[CH2:12]([N:19]1[CH2:24][CH2:23][O:22][CH:21]([C:25]2[CH:30]=[CH:29][C:28](Br)=[CH:27][CH:26]=2)[CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Cu]I>[CH2:12]([N:19]1[CH2:24][CH2:23][O:22][CH:21]([C:25]2[CH:30]=[CH:29][C:28]([O:9][C:3]3[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=3[CH3:1])=[CH:27][CH:26]=2)[CH2:20]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 113352,6-DimethylphenolHCID 24758Sodium hydrideHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 580978794-Benzyl-2-(4-bromo-phenyl)-morpholine

Product 1

HCID 66653950HCID 66653950, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent2×

Procedure

2,6-Dimethylphenol was added portionwise to a suspension of NaH (272 mg, 60% in oil, 6.8 mmol) in toluene (15 mL). After complete addition the mixture was heated under reflux for 15 min. and subsequently cooled to room temperature. To the resulting mixture was added a solution of 4-benzyl-2-(4-bromo-phenyl)-morpholine (1.5 g, 4.5 mmol) in toluene (10 mL), followed by copper(I) iodide (438 mg, 2.3 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.48 mL, 2.3 mmol), and cesium carbonate (2.96 g, 9.1 mmol). The obtained mixture was heated under reflux for 3 days. After cooling to room temperature, the mixture was partitioned between EtOAc and water. The layers were separated. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (EtOAc:heptanes 5:95) to afford 4-benzyl-2-[4-(2,6-dimethyl-phenoxy)-phenyl]-morpholine (1.2 g), which was used as such in the next step.

Workup

  1. additionAfter complete addition the mixture
  2. temperaturewas heated
  3. temperatureunder reflux for 15 min.
  4. temperatureThe obtained mixture was heated
  5. temperatureunder reflux for 3 days
  6. temperatureAfter cooling to room temperature
  7. customthe mixture was partitioned between EtOAc and water
  8. customThe layers were separated
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by column chromatography (EtOAc:heptanes 5:95)

Sources & evidence

ORD record
ord-2614a90324264ab8bfb75ed26cef3e0a
Source dataset
uspto-grants-2016_01
Patent number
US09227960B2

Reaction notes

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