Trifluoroacetic acid → 3-Chloro-5-fluoro-4-(1,2,3,6-tetrahydropyridin-4-yl)pyridine

HRID 524956Notes

Reaction equation

HRID 524956 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[CH:10]=[N:11][CH:12]=[C:13]([F:28])[C:14]=1[C:15]1[CH2:16][CH2:17][N:18](C(OC(C)(C)C)=O)[CH2:19][CH:20]=1>C(Cl)Cl>[Cl:8][C:9]1[CH:10]=[N:11][CH:12]=[C:13]([F:28])[C:14]=1[C:15]1[CH2:16][CH2:17][NH:18][CH2:19][CH:20]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86721011tert-butyl 4-(3-chloro-5-fluoro-4-pyridyl)-3,6-dihydro-2H-pyridine-1-carboxylate

Product 1

HCID 867210123-Chloro-5-fluoro-4-(1,2,3,6-tetrahydropyridin-4-yl)pyridineYield 97.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (2 mL, 25.96 mmol) was added to a stirred solution of tert-butyl 4-(3-chloro-5-fluoro-4-pyridyl)-3,6-dihydro-2H-pyridine-1-carboxylate (708 mg, 2.264 mmol) in DCM (10 mL) and the reaction stirred at ambient temperature for 2 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The residue was passed through a 10 g SCX-2 cartridge and washed with MeOH/DCM mixtures. The product was eluted by washing the cartridge with 2M NH3 in MeOH/DCM mixtures and concentrated in vacuo to give 3′-chloro-5′-fluoro-1,2,3,6-tetrahydro-4,4′-bipyridine as an off-white solid (468 mg, 97% Yield). MS (ES+) 213.1.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue azeotroped with DCM (×2) and ether (×2)
  3. washwashed with MeOH/DCM
  4. washThe product was eluted
  5. washby washing the cartridge with 2M NH3 in MeOH/DCM mixtures
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-648ad3802b654ec196b6bbba0792dccc
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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