Potassium Carbonate → 1-(1-(3-Methoxy-4-nitrophenyl)piperidin-4-yl)-4-methylpiperazine
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
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 (0-15% 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, 2H), 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, 7H), 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
- temperatureAfter cooling
- concentrationthe reaction mixture was concentrated
- customthe residue partitioned between ethyl acetate and brine
- extractionThe aqueous phase was extracted with ethyl acetate
- concentrationThe combined organic phases were concentrated
- customThe residue was separated by flash chromatography (0-15% 2% ammonium hydroxide MeOH solution in dichloromethane)
Sources & evidence
- ORD record
- ord-481e0f16f8264117a1696327715a9ecb
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08435980B2
Reaction notes
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