3,5-Dibromopyridine → Tert-butyl 4-(5-bromopyridin-3-yl)piperazine-1-carboxylate

HRID 2277718Notes

Reaction equation

HRID 2277718 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19](Br)[CH:20]=1.CC(C)([O-])C.[Na+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:19]2[CH:18]=[N:17][CH:16]=[C:15]([Br:14])[CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 693693,5-DibromopyridineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 11653049Tert-butyl 4-(5-bromopyridin-3-yl)piperazine-1-carboxylateYield 54%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of piperazine-1-carboxylic acid tert-butyl ester (1.86 g, 10 mmol), 3,5-dibromopyridine (2.37 g, 10 mmol), palladium(II) acetate (0.11 g, 0.5 mmol), anphos (0.35 g, 0.6 mmol), and sodium tert-butoxide (1.68 g, 15 mmol) in dioxane (10 mL) was heated at 130° C. in a microwave reactor for 2 hours. The mixture was then diluted with water, and extracted with EtOAc. The organic layer was dried over anhy. Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (eluent with ethyl acetate:hexane=1:5) to afford the title compound as a white solid (1.84 g, 54%). MS: 342.2 (M+).

Workup

  1. extractionextracted with EtOAc
  2. customThe organic layer was dried over anhy
  3. filtrationNa2SO4, filtered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography (eluent with ethyl acetate:hexane=1:5)

Sources & evidence

ORD record
ord-3a2bd08742fa410281012d5d0d629ce5
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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