3-Fluoroaniline → HCID 46938834, compound

HRID 388536Notes

Reaction equation

HRID 388536 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].C[Si]([C:27]#[N:28])(C)C.[OH-].[NH4+]>C(O)(=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:19][C:18]2[CH:20]=[CH:21][CH:22]=[C:16]([F:15])[CH:17]=2)([C:27]#[N:28])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 97423-FluoroanilineHCID 14923Ammonium HydroxideHCID 192201-Benzyl-4-piperidoneHCID 82115Trimethylsilyl cyanide

Product 1

HCID 46938834HCID 46938834, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 1-benzyl-4-piperidinone (25.0 g, 132 mmol) in acetic acid (132 ml) at 0° C. were added 3-fluoroaniline (12.7 ml, 132 mmol) and trimethylsilyl cyanide (17.6 ml, 132 mmol) dropwise. The reaction was allowed to warm to rt and stir for 18 h. The reaction was poured onto a mixture of ice (200 g) and ammonium hydroxide (200 ml), and the product was extracted with dichloromethane (4×500 ml). The combined organic extractions were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give a brown solid. The crude material was recrystallized from diethyl ether to afford 1-benzyl-4-[(3-fluorophenyl)amino]piperidine-4-carbonitrile as a beige solid (67%). LCMS. (M+H) 310.1. 1H NMR (400 MHz, DMSO) δ 7.33 (m, 4H), 7.25 (m, 1H), 7.19 (q, J=7.8 Hz, 1H), 6.66 (dd, J=8.2, 2.0 Hz, 1H), 6.59 (dt, J=12.2, 2.2 Hz, 1H), 6.50 (td, J=8.5, 2.2 Hz, 1H), 6.42 (s, 1H), 3.52 (s, 2H), 2.76 (d, J=11.2 Hz, 2H), 2.30 (t, J=10.9 Hz, 4H), 1.82 (t, J=10.5 Hz, 2H).

Workup

  1. extractionthe product was extracted with dichloromethane (4×500 ml)
  2. extractionThe combined organic extractions
  3. washwere washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a brown solid
  8. customThe crude material was recrystallized from diethyl ether

Sources & evidence

ORD record
ord-44cdf70376254dec847f9612f61c6097
Source dataset
uspto-grants-2013_02
Patent number
US08377954B2

Reaction notes

Loading…