Potassium Carbonate → (R)-tert-Butyl 2-Methyl-4-(6-nitropyridin-3-yl)piperazine-1-carboxylate

HRID 1026411Notes

Reaction equation

HRID 1026411 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@@H:12]1[CH2:17][NH:16][CH2:15][CH2:14][N:13]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:11][C@@H:12]1[CH2:17][N:16]([C:2]2[CH:7]=[N:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:15][CH2:14][N:13]1[C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 8176205-Bromo-2-nitropyridineHCID 10262201tert-Butyl (2R)-2-methylpiperazine-1-carboxylate

Product 1

HCID 49840311(R)-tert-Butyl 2-Methyl-4-(6-nitropyridin-3-yl)piperazine-1-carboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
65 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with methylsulfinylmethane (50 mL), 5-bromo-2-nitropyridine (2.2 g, 11 mmol), (R)-tert-butyl 2-methylpiperazine-1-carboxylate (2.2 g, 11 mmol), and potassium carbonate (3.08 g, 22 mmol). See FIG. 8. The system was subjected to three cycles of vacuum/nitrogen flush and heated at 65° C. for 15 h. It was then cooled to room temperature, and partitioned between ethyl acetate (100 mL) and water (20 mL). The aqueous layer was separated and extracted with ethyl acetate (50 mL×2). The combined organic layer was washed with brine (50 mL) and dried over anhydrous sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flash column chromatography eluting with 2:1 (UV) petroleum/ethyl acetate to afford 108a as a yellow solid (1.75 g, 50%). LCMS: [M+H]+ 323

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customflush
  3. temperatureIt was then cooled to room temperature
  4. custompartitioned between ethyl acetate (100 mL) and water (20 mL)
  5. customThe aqueous layer was separated
  6. extractionextracted with ethyl acetate (50 mL×2)
  7. washThe combined organic layer was washed with brine (50 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe drying agent was removed by filtration
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified on flash column chromatography
  12. washeluting with 2:1 (UV) petroleum/ethyl acetate

Sources & evidence

ORD record
ord-428e88a81a084fef8c6e4cdfaca32c99
Source dataset
uspto-grants-2014_05
Patent number
US08729072B2

Reaction notes

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