4-Bromopyridinium chloride → tert-butyl 4-(1-(pyridin-4-yl)-1H-indol-6-yl)piperazine-1-carboxylate

HRID 240835Notes

Reaction equation

HRID 240835 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N:10]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]3)[CH:8]=2)[CH:3]=[CH:2]1.CC(C)([O-])C.[Na+].Cl.Br[C:31]1[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=1>[C].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[N:34]1[CH:35]=[CH:36][C:31]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([N:10]4[CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15]4)[CH:8]=3)[CH:3]=[CH:2]2)=[CH:32][CH:33]=1

Participants

7

Reactant 3

HCID 881004-Bromopyridinium chlorideHCID 23676156Sodium t-butoxideHCID 59781270tert-butyl 4-(1H-indol-6-yl)piperazine-1-carboxylate

Product 1

HCID 58159626tert-butyl 4-(1-(pyridin-4-yl)-1H-indol-6-yl)piperazine-1-carboxylateYield 59%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 178418390HCID 178418390, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl 4-(1H-indol-6-yl)piperazine-1-carboxylate (500 mg, 1.66 mmol), sodium tert-butoxide (447 mg, 4.65 mmol), 4-bromopyridine hydrochloride (355 mg, 1.83 mmol) and toluene (11 mL) were sequentially acted to a reactor. Then, the gas dissolved in the mixture was removed using ultrasonic waves and nitrogen gas. After adding 10% (w/w) palladium-carbon (Pd—C, 177 mg, 0.083 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 52 mg, 0.083 mmol), the mixture was stirred at 100° C. for 24 hours in a sealed state. After cooling to room temperature and filtering using a diatomite pad, water was added and the mixture was extracted with ethyl acetate. The collected organic layer was washed with brine and concentrated under reduced pressure by drying with anhydrous sodium sulfate. The residue was purified by chromatography (silica gel, EA:Hx=1:1→EA only). The target compound (369 mg, 59%) was obtained as white solid.

Workup

  1. dissolutionThen, the gas dissolved in the mixture
  2. customwas removed
  3. temperatureAfter cooling to room temperature
  4. filtrationfiltering
  5. additionwas added
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe collected organic layer was washed with brine
  8. concentrationconcentrated under reduced pressure
  9. dry with materialby drying with anhydrous sodium sulfate
  10. customThe residue was purified by chromatography (silica gel, EA

Sources & evidence

ORD record
ord-70ea6b8103da48dfa4d133cdd7bfe4a3
Source dataset
uspto-grants-2014_02
Patent number
US08648089B2

Reaction notes

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