Water → 1-[1-(2-Fluoroethyl)-4-piperidinyl]-4-[3-(methyloxy)-4-nitrophenyl]piperazine

HRID 419396Notes

Reaction equation

HRID 419396 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:12]2[CH2:17][CH2:16][N:15]([CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].C([O-])([O-])=O.[Na+].[Na+].I[CH:31]([F:33])[CH3:32].O>C(#N)C>[F:33][CH2:31][CH2:32][N:21]1[CH2:22][CH2:23][CH:18]([N:15]2[CH2:14][CH2:13][N:12]([C:5]3[CH:6]=[CH:7][C:8]([N+:9]([O-:11])=[O:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:17][CH2:16]2)[CH2:19][CH2:20]1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 23510620IodofluoroethaneHCID 594529341-[3-(Methyloxy)-4-nitrophenyl]-4-(4-piperidinyl)piperazine

Product 1

HCID 594528511-[1-(2-Fluoroethyl)-4-piperidinyl]-4-[3-(methyloxy)-4-nitrophenyl]piperazineYield 88%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 1-[3-(methyloxy)-4-nitrophenyl]-4-(4-piperidinyl)piperazine (Example 89, step D) (0.958 g, 2.99 mmol) and Na2CO3 (0.470 g, 4.43 mmol) in acetonitrile (20 mL) was added iodofluoroethane (0.500 mL, 6.15 mmol) in one portion. The resultant mixture was heated at 70° C. for 48 h. When complete by TLC, the reaction was poured into H2O (150 mL), extracted with DCM and EtOAc, dried (MgSO4) and concentrated. Purification by flash chromatography provided the title compound of step A (0.972 g, 2.63 mmol, 88%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.32-1.43 (m, 2H), 1.70 (d, J=15.0 Hz, 2H), 1.94 (t, J=12.5 Hz, 2H), 2.12-2.21 (m, 1H), 2.50 (t, J=5.0 Hz, 1H), 2.52-2.58 (m, 5H), 2.88 (d, J=10.4 Hz, 2H), 3.35-3.40 (m, 4H), 3.86 (s, 3H), 4.46 (dt, JHF=47.8 Hz, J=4.9 Hz, 2H), 6.47 (d, J=2.4 Hz, 1H), 6.54 (dd, J=9.3, 2.1 Hz, 1H), 7.83 (d, J=9.3 Hz, 1H).

Workup

  1. extractionextracted with DCM and EtOAc
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customPurification by flash chromatography

Sources & evidence

ORD record
ord-625ac38fb8c44fa397d1a511973bee31
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

Loading…