Trifluoroacetic acid → N-[4-Fluoro-3-(methyloxy)phenyl]-4-piperidinamine

HRID 906346Notes

Reaction equation

HRID 906346 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)=[CH:4][C:3]=1[O:22][CH3:23].C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]2)=[CH:4][C:3]=1[O:22][CH3:23]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 576995241,1-Dimethylethyl 4-{[4-fluoro-3-(methyloxy)phenyl]amino}-1-piperidinecarboxylate

Product 1

HCID 57699516N-[4-Fluoro-3-(methyloxy)phenyl]-4-piperidinamineYield 99.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1,1-dimethylethyl 4-{[4-fluoro-3-(methyloxy)phenyl]amino}-1-piperidinecarboxylate (D9) (1.45 g, 4.48 mmol) in DCM (16 ml) was cooled in an ice bath and TFA (4 ml) was added. The reaction mixture was stirred for 1 h, then warmed to room temperature and stirred for 2 h. The solvent was removed in vacuo and the residue partitioned between EtOAc and saturated aqueous NaHCO3 solution. The organic phase was washed with further saturated aqueous NaHCO3 solution. The aqueous was concentrated to ˜50% volume, further basified with 2M NaOH solution and extracted with EtOAc (×2). All organic phases were combined and washed with further 2M NaOH solution, dried and concentrated to give the title compound as an orange gum (1 g). δH (DMSO-d6, 400 MHz) 6.86 (1H, dd), 6.33 (1H, dd), 6.03 (1H, m), 5.32 (1H, d), 3.74 (3H, s), 3.33 (1H, br s), 3.18 (1H, m), 2.92 (2H, m), 2.51 (2H, m), 1.83 (2H, m), 1.17 (2H, m). MS (ES): MH+ 225.

Workup

  1. stirringstirred for 2 h
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between EtOAc and saturated aqueous NaHCO3 solution
  4. washThe organic phase was washed with further saturated aqueous NaHCO3 solution
  5. concentrationThe aqueous was concentrated to ˜50% volume
  6. extractionextracted with EtOAc (×2)
  7. washwashed with further 2M NaOH solution
  8. customdried
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-ba117623887545ee92f4d9acafb1af18
Source dataset
uspto-grants-2011_09
Patent number
US08012981B2

Reaction notes

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