Morpholine → 4-(4-Bromobenzyl)morpholine

HRID 1670745Notes

Reaction equation

HRID 1670745 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 685274-Bromobenzyl bromide

Product 1

HCID 7835034-(4-Bromobenzyl)morpholine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-Bromobenzyl bromide (Aldrich Co., 2.0 g) and morpholine (0.73 ml) were dissolved in acetonitrile (15 ml), potassium carbonate (1.3 g) was added, and the mixture was heated under reflux for 4 hr. The insoluble material was filtered off, and the filtrate was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (5:1)) to give 4-(4-bromobenzyl)morpholine (1.55 g). 4-(4-Bromobenzyl)morpholine (1.55 g), 1-(tert-butoxycarbonyl)piperazine (1.27 g), 2-(di-tert-butylphosphino)biphenyl (37 mg), tris(dibenzylideneacetone)dipalladium (57 mg) and sodium tert-butoxide (1.2 g) were added to toluene (13 ml), and the mixture was heated under reflux for 5 hr. The insoluble material was filtered through a Celite (trademark) filter, and the filtrate was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography. The obtained 4-[4-(morpholine-4-ylmethyl)phenyl]piperazine-1-carboxylic acid tert-butyl ester was dissolved in dichloromethane, trifluoroacetic acid was added and the mixture was stirred overnight at room temperature. The mixture was neutralized with an aqueous sodium hydroxide solution, and extracted with dichloromethane. The organic layer was dried and the solvent was evaporated under reduced pressure to give 4-(4-piperazin-1-ylbenzyl)morpholine (1.06 g, yield 51%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4 hr
  3. filtrationThe insoluble material was filtered off
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (5:1))

Sources & evidence

ORD record
ord-8455a7d214ba4107bd6c5b9b50e4d938
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Reaction notes

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