Cesium carbonate → HCID 86683761, compound

HRID 519378Notes

Reaction equation

HRID 519378 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.[CH3:11][C:12]1([CH3:25])[NH:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH3:11][C:12]1([CH3:25])[N:17]([C:2]2[CH:7]=[N:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 8176205-Bromo-2-nitropyridineHCID 227103871-Boc-3,3-dimethylpiperazine

Product 1

HCID 86683761HCID 86683761, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 5-bromo-2-nitropyridine (5.6 g, 28.0 mmol), tert-butyl 3,3-dimethyl-piperazine-1-carboxylate (3.0 g, 14.0 mmol), cesium carbonate (9.1 g, 28 mmol), and 1,4-dioxane (50 mL). After bubbling nitrogen through the resulting solution for 30 min, Binap (870 mg, 1.4 mmol) and tris(dibenzylideneacetone)dipalladium(0) (1.2 g, 1.4 mmol) were added. The reaction mixture was subjected to three cycles of vacuum/argon flush and stirred at 120° C. for 24 h. After this time the reaction was cooled to room temperature it was filtered and the filtrate was partitioned between ethyl acetate (200 mL) and water (50 mL). The aqueous layer was separated and extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (50 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 5:1 petroleum ether/ethyl acetate to afford 125a (1.27 g, 27%). LCMS: [M+H]+ 337.2.

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the resulting solution for 30 min
  3. customflush
  4. temperatureAfter this time the reaction was cooled to room temperature it
  5. filtrationwas filtered
  6. customthe filtrate was partitioned between ethyl acetate (200 mL) and water (50 mL)
  7. customThe aqueous layer was separated
  8. extractionextracted with ethyl acetate (3×50 mL)
  9. washThe combined organic layer was washed with brine (50 mL)
  10. dry with materialdried over sodium sulfate
  11. customThe drying agent was removed by filtration
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customThe residue was purified by silica-gel column chromatography
  14. washeluting with 5:1 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-822838e2e6fc4aecaf24fb849f3d6e0b
Source dataset
uspto-grants-2015_08
Patent number
US09115152B2

Reaction notes

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