tert-Butyl piperazine-1-carboxylate → tert-butyl 4-(1H-indol-6-yl)piperazine-1-carboxylate

HRID 240831Notes

Reaction equation

HRID 240831 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[C:15]1[CH:23]=[C:22]2[C:18]([CH:19]=[CH:20][NH:21]2)=[CH:17][CH:16]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C1COCC1>[NH:21]1[C:22]2[C:18](=[CH:17][CH:16]=[C:15]([N:4]3[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]3)[CH:23]=2)[CH:19]=[CH:20]1

Participants

7

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 6764936-BromoindoleHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 59781270tert-butyl 4-(1H-indol-6-yl)piperazine-1-carboxylateYield 43.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Pd2(dba)3 (30 mg, 0.026 mmol), tert-butyl piperazine-1-carboxylate (570 mg, 3.06 mmol), X-Phos (CAS Number: 564483-18-7, 40 mg, 0.077 mmol) and 6-bromo-1H-indole (500 mg, 2.55 mmol) were added to THF (2 mL) in a sealed reactor. After adding lithium hexamethyldisilazide (LHMDS; 1 M in THF, 5.61 mL, 5.6 mmol) at room temperature, the mixture solution was stirred at 65° C. for 24 hours in a sealed state. After cooling to room temperature, the reaction was terminated with saturated ammonium chloride aqueous solution. After extraction with ethyl acetate, the collected organic layer was washed with saturated sodium bicarbonate aqueous solution and brine and then concentrated by drying with anhydrous sodium sulfate. The residue was purified by chromatography (silica gel, EA:Hx=1:2). The target compound (334 mg) was obtained as white solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction was terminated with saturated ammonium chloride aqueous solution
  3. extractionAfter extraction with ethyl acetate
  4. washthe collected organic layer was washed with saturated sodium bicarbonate aqueous solution and brine
  5. concentrationconcentrated
  6. dry with materialby drying with anhydrous sodium sulfate
  7. customThe residue was purified by chromatography (silica gel, EA:Hx=1:2)

Sources & evidence

ORD record
ord-6e1ef6731cd547e1ab7cac589ef4ff4e
Source dataset
uspto-grants-2014_02
Patent number
US08648089B2

Reaction notes

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