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 644953Notes

Reaction equation

HRID 644953 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}-3,6dihydropyridine-1-carboxylate (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®, the filtrate evaporated and the residue partitioned between methylene chloride and 1N sodium hydroxide. The organic phase 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) title compound 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. customthe filtrate evaporated
  6. customthe residue partitioned between methylene chloride and 1N sodium hydroxide
  7. customThe organic phase was separated
  8. extractionthe aqueous phase was re-extracted twice with methylene chloride
  9. washThe combined organic extracts were washed with water, brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6f91e7a3dea641da8b5fdcaeaa2deb23
Source dataset
uspto-grants-2010_04
Patent number
US07700778B2

Reaction notes

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