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

HRID 883767ノート

反応式

HRID 883767 の反応式
[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]

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-8c366d2f332843359442afffe2adc62c
出典データセット
uspto-grants-2012_08
特許番号
US08236953B2

反応ノート

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