Tert-Butyl 4-{4-Chloro-2-[(1S)-1-(Azido)Ethyl]Phenyl}-3,6-Dihydropyridine-1-Carboxylate → Tert-Butyl 4-{2-[(1S)-1-Aminoethyl]-4-Chlorophenyl]Piperidine-1-Carboxylate

HRID 2415556Notes

Reaction equation

HRID 2415556 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH:13]=2)=[C:4]([C@@H:21]([N:23]=[N+]=[N-])[CH3:22])[CH:3]=1>C(O)C.[Pt](=O)=O>[NH2:23][C@H:21]([C:4]1[CH:3]=[C:2]([Cl:1])[CH:7]=[CH:6][C:5]=1[CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:10][CH2:9]1)[CH3:22]

Participants

4

Reactant 1

HCID 23525647Tert-Butyl 4-{4-Chloro-2-[(1S)-1-(Azido)Ethyl]Phenyl}-3,6-Dihydropyridine-1-Carboxylate

Product 1

HCID 68518377Tert-Butyl 4-{2-[(1S)-1-Aminoethyl]-4-Chlorophenyl]Piperidine-1-Carboxylate

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 702EthanolSolvent

Procedure

A mixture of tert-butyl 4-{4-chloro-2-[(1S)-1-(azido)ethyl]phenyl}-3,6-dihydropyridine-1-carboxylate (3-6) (22.9 g, 63.1 mmol) and platinum (IV) oxide (1.08 g, 4.73 mmol) in ethanol/glacial acetic acid (1:1, 200 mL) was hydrogenated at atmospheric pressure for approximately 15 h. The resulting mixture was degassed via three vacuum/hydrogen ingress cycles to remove the liberated nitrogen and the hydrogenation was then continued for a further 24 h. The reaction mixture was filtered through a short column of celite®, eluted copiously with ethanol. The filtrate was evaporated and the residue was partitioned between methylene chloride and 1N sodium hydroxide. The organic layer was separated and the aqueous phase was re-extracted twice with methylene chloride. The combined organic extracts were washed with water, brine, dried (Na2SO4), and concentrated in vacuo to give crude (˜70% pure) 3-7 as a colorless foam.

Workup

  1. customThe resulting mixture was degassed via three vacuum/hydrogen ingress cycles
  2. customto remove the liberated nitrogen
  3. waitthe hydrogenation was then continued for a further 24 h
  4. filtrationThe reaction mixture was filtered through a short column of celite®
  5. washeluted copiously with ethanol
  6. customThe filtrate was evaporated
  7. customthe residue was partitioned between methylene chloride and 1N sodium hydroxide
  8. customThe organic layer was separated
  9. extractionthe aqueous phase was re-extracted twice with methylene chloride
  10. washThe combined organic extracts were washed with water, brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6ca7a598dea74ab89398e0f148efe8ba
Source dataset
uspto-grants-2004_11
Patent number
US06818658B2

Reaction notes

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