tert-Butyl piperazine-1-carboxylate → HCID 66760215, compound

HRID 1850388Notes

Reaction equation

HRID 1850388 reaction equation
CC(C)([O-])C.[Na+].[CH3:7][C:8]1([CH3:27])[C:12](=[O:13])[C:11]2[C:14]([CH3:26])=[C:15]([N:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[C:16]([CH3:19])=[C:17]([CH3:18])[C:10]=2[O:9]1.[C:28](N1CCNCC1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:7][C:8]1([CH3:27])[C:12](=[O:13])[C:11]2[C:14]([CH3:26])=[C:15]([N:20]3[CH2:21][CH2:22][N:23]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:25]3)[C:16]([CH3:19])=[C:17]([CH3:18])[C:10]=2[O:9]1

Participants

8

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 66759817HCID 66759817, compound

Product 1

HCID 66760215HCID 66760215, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium t-butoxide (13.45 g, 140 mmol) was added to a mixture of toluene (300 mL) containing 4-(2,2,4,6,7-pentamethyl-3-oxo-2,3-dihydro-1-benzofuran-5-yl)piperazine (28.32 g, 100 mmol) synthesized in Reference Example 36, N-Boc-piperazine (22.35 g, 120 mmol), palladium acetate (448 mg, 2 mmol) and BINAP (3.74 g, 6 mmol) at room temperature, and the mixture was heated to reflux under argon atmosphere. After a reaction for 16 hours, it was cooled to room temperature and diluted with ethyl acetate. The organic layer was washed with saturated saline, and then dried using anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel chromatography (hexane-ethyl acetate 9:1 to 4:1), and recrystallized from hexane to give 20.5 g of the title compound (yield: 53%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux under argon atmosphere
  3. customAfter a reaction for 16 hours
  4. washThe organic layer was washed with saturated saline
  5. customdried
  6. customThe solvent was removed under reduced pressure
  7. customThe residue was purified by silica gel chromatography (hexane-ethyl acetate 9:1 to 4:1)
  8. customrecrystallized from hexane

Sources & evidence

ORD record
ord-0412b97485fc4edcbea285048d429ec9
Source dataset
uspto-grants-2015_02
Patent number
US08957069B2

Reaction notes

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