4-Bromopyridinium chloride → HCID 69426437, compound

HRID 1592861Notes

Reaction equation

HRID 1592861 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.BrC1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1.[CH3:25]C(C)([O-])C.[Na+]>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:15]([CH3:25])[C:16]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 881004-Bromopyridinium chlorideHCID 21934652tert-Butyl 4-((methylamino)methyl)piperidine-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 69426437HCID 69426437, compoundYield 91.1%

Reagents, catalysts & solvents 3

HCID 83681Tris(1,1-dimethylethyl)phosphineCatalystHCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 1-t-butoxycarbonyl-4-[(methylamino)methyl]piperidine (4.28 g, 18.8 mmol), 4-bromopyridine hydrochloride (4.82 g, 22.5 mmol) in 1,4-dioxane (60 mL) is degassed by sonication and passing argon through the mixture for 15 minutes. Sodium t-butoxide (5.77 g, 60.0 mmol), tris(dibenzylideneacetone) dipalladium (858 mg, 0.938 mmol) and tri-t-butyl phosphine (0.5M in toluene; 3 mL, 1.50 mmol) are added sequentially. The system is sealed, evacuated and back-filled with argon (×5), then heated at 60° C. for 48 hours. The mixture is poured onto a 1:1 mixture of water-ethyl acetate (4 mL), Celite™ is added and the mixture is filtered through a bed of Celite™. The phases are separated and the aqueous phase is extracted into ethyl acetate (×3). The combined organic extracts are washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue is emulsified in water, potassium hydrogen sulfate is added until pH 2-3 and the aqueous phase is washed with ethyl acetate (×3). The aqueous phase is made basic by the addition of sodium hydroxide until pH >12 and extracted into ethyl acetate (×4). The combined organic extracts are washed with brine, dried (magnesium sulfate), filtered and concentrated in vacuo giving 1-t-butoxycarbonyl-4-{[(methyl)(pyridin-4-yl)amino]methyl}piperidine (5.23 g, 91%).

Workup

  1. customis degassed by sonication
  2. customfor 15 minutes
  3. customThe system is sealed
  4. customevacuated
  5. additionback-filled with argon (×5)
  6. additionThe mixture is poured onto a 1:1 mixture of water-ethyl acetate (4 mL), Celite™
  7. additionis added
  8. filtrationthe mixture is filtered through a bed of Celite™
  9. customThe phases are separated
  10. extractionthe aqueous phase is extracted into ethyl acetate (×3)
  11. washThe combined organic extracts are washed with brine
  12. dry with materialdried (sodium sulfate)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. additionpotassium hydrogen sulfate is added until pH 2-3
  16. washthe aqueous phase is washed with ethyl acetate (×3)
  17. additionThe aqueous phase is made basic by the addition of sodium hydroxide until pH >12
  18. extractionextracted into ethyl acetate (×4)
  19. washThe combined organic extracts are washed with brine
  20. dry with materialdried (magnesium sulfate)
  21. filtrationfiltered
  22. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ee85760d9bc74943a4a41e0012377a60
Source dataset
uspto-grants-2007_11
Patent number
US07294627B2

Reaction notes

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