tert-Butyl piperazine-1-carboxylate → HCID 23149794, compound

HRID 1670746Notes

Reaction equation

HRID 1670746 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.C(OC([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=O)(C)(C)C.CC(C)([O-])C.[Na+]>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=CC=CC=1)(C)(C)C.C1(C)C=CC=CC=1>[N:22]1([C:2]2[CH:14]=[CH:13][C:5]([CH2:6][N:7]3[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)=[CH:4][CH:3]=2)[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1

Participants

7

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 7835034-(4-Bromobenzyl)morpholineHCID 23676156Sodium t-butoxide

Product 1

HCID 23149794HCID 23149794, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 27342152-(Di-tert-butylphosphino)biphenylCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

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 5 hr
  3. filtrationThe insoluble material was filtered through a Celite (trademark)
  4. filtrationfilter
  5. customthe filtrate was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography
  7. dissolutionThe obtained 4-[4-(morpholine-4-ylmethyl)phenyl]piperazine-1-carboxylic acid tert-butyl ester was dissolved in dichloromethane
  8. additiontrifluoroacetic acid was added
  9. extractionextracted with dichloromethane
  10. customThe organic layer was dried
  11. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-560dd92fa6994bd08985d54d3bdcc838
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Reaction notes

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