Potassium Carbonate → 1-(1-(3-Methoxy-4-nitrophenyl)piperidin-4-yl)-4-methylpiperazine

HRID 390111Notes

Reaction equation

HRID 390111 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH2:4][CH2:3]1.F[C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17]([O:24][CH3:25])[CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:25][O:24][C:17]1[CH:16]=[C:15]([N:11]2[CH2:12][CH2:13][CH:8]([N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)[CH2:9][CH2:10]2)[CH:20]=[CH:19][C:18]=1[N+:21]([O-:23])=[O:22]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 7957071-Methyl-4-(piperidin-4-yl)piperazineHCID 27792505-Fluoro-2-nitroanisole

Product 1

HCID 567772491-(1-(3-Methoxy-4-nitrophenyl)piperidin-4-yl)-4-methylpiperazineYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 1-methyl-4-(piperidin-4-yl)piperazine (4.2 g, 22.91 mmol) in anhydrous DMF (40 mL) was added 4-fluoro-2-methoxy-1-nitrobenzene (3.92 g, 22.91 mmol) and potassium carbonate (3.80 g, 27.5 mmol). This suspension was heated at 70° C. overnight. After cooling, the reaction mixture was concentrated, and the residue partitioned between ethyl acetate and brine. The aqueous phase was extracted with ethyl acetate. The combined organic phases were concentrated. The residue was separated by flash chromatography (eluted with 0-15% of 2% ammonium hydroxide MeOH solution in dichloromethane) to give 6.88 g of the title compound. Yield: 90%. MS (DCI) m/z 335 (M+H)+; 1H NMR (300 MHz, CDCl3): δ 1.58-1.68 (m, 2H), 1.93-1.99 (m, J=11.53 Hz, 2 H), 2.29 (s, 3H), 2.44-2.51 (m, 4H), 2.62 (s, 4H), 2.92-3.02 (m, 2H), 3.90-3.98 (m, 7 H), 6.31 (d, J=2.37 Hz, 1H), 6.42 (dd, J=9.32, 2.54 Hz, 1H), 7.99 (d, J=9.49 Hz, 1H).

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated
  3. customthe residue partitioned between ethyl acetate and brine
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. concentrationThe combined organic phases were concentrated
  6. customThe residue was separated by flash chromatography (eluted with 0-15% of 2% ammonium hydroxide MeOH solution in dichloromethane)

Sources & evidence

ORD record
ord-b884c7b8681240378715863b3faa5e37
Source dataset
uspto-grants-2013_02
Patent number
US08383624B2

Reaction notes

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