Sodium Iodide → HCID 22321629, compound

HRID 496613Notes

Reaction equation

HRID 496613 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH2:8][CH2:9]OS(C)(=O)=O.[C:15]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].C([O-])([O-])=O.[K+].[K+].[Na+].[I-].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O.C(OCC)(=O)C.C(OCC)C>[C:15]([N:22]1[CH2:23][CH2:24][N:25]([CH2:9][CH2:8][C:7]2[CH:6]=[CH:5][N:4]=[CH:3][C:2]=2[F:1])[CH2:26][CH2:27]1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16]

Participants

10

Reactant 5

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 22321653HCID 22321653, compound

Product 1

HCID 22321629HCID 22321629, compoundYield 84.6%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

3-Fluoro-4-(2-methanesulfonyloxyethyl)pyridine (5.2 g, 23.7 mmol) was dissolved in DMF (65 mL). 1-Boc-piperazine (8.85 g, 47.4 mmol), K2CO3 (3.3 g, 23.7 mmol), NaI (3.6 g, 23.7 mmol) and Cs2CO3 (7.7 g, 23.7 mmol) were added, and the mixture heated to 55° C. for 18 h. The mixture was cooled to room temperature and diluted with water and ethyl acetate. The layers were separated, and the water layer extracted with ethyl acetate. The organic layers were combined, washed with brine, dried (Na2SO4), filtered, and concentrated under vacuum to provide a solution of product and DMF. The residue was dissolved in diethyl ether and water. The layers were separated, and the water layer extracted with diethyl ether. The organic layers were combined, washed with brine, dried (Na2SO4), filtered, and concentrated under vacuum. The crude product was purified by chromatography (SiO2, 15:1-6:1 CH2Cl2:CMA) to give 1-Boc-4-[2-(3-fluoropyridin-4-yl)ethyl]piperazine (6.2 g, 84%).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customThe layers were separated
  3. extractionthe water layer extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customto provide a solution of product and DMF
  9. customThe layers were separated
  10. extractionthe water layer extracted with diethyl ether
  11. washwashed with brine
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated under vacuum
  15. customThe crude product was purified by chromatography (SiO2, 15:1-6:1 CH2Cl2:CMA)

Sources & evidence

ORD record
ord-d29033116ea44013bdf244224f738147
Source dataset
uspto-grants-2005_09
Patent number
US06946467B2

Reaction notes

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