1-Fluoro-3-nitrobenzene → 1-Methyl-4-(3-nitrophenyl)piperazine

HRID 1989042Notes

Reaction equation

F[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:17][N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1>CS(C)=O.O>[CH3:17][N:18]1[CH2:23][CH2:22][N:21]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[CH:3]=2)[CH2:20][CH2:19]1

Participants

Conditions

Temperature: 122 °C

Procedure

To a suspension of 1-fluoro-3-nitrobenzene (3.77 mL, 35.4 mmol) and potassium carbonate (10 g, 71 mmol) in DMSO (30 mL) was added 1-methyl piperazine (59 mL, 53.2 mmol). The mixture was stirred at 122° C. for 24 hours. After cooing down, the mixture was diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried with sodium sulfate (Na2SO4), and concentrated in vacuo to afford an orange oil. Recrystallization from EtOAc/hexanes gave 4.2 g of 1-(4-methyl-piperazin-1-yl)-3-nitrobenzene, which was reduced via hydrogenation to give the title compound (beige solid, 3 g). 1H NMR (400 MHz, CDCl3) δ (ppm): 7.04 (t, J=8.0 Hz, 1H), 6.38 (dd, J=2.3, 8.2 Hz, 1H), 6.26 (t, J=2.2 Hz, 1H), 6.22 (dd, J=2.3, 8.2 Hz, 1H), 3.60 (br, 2H), 3.18 (t, J=4.9 Hz, 4H), 2.55 (t, J=4.9 Hz, 4H), 2.34 (s, 3H).

Workup

extractionextracted with EtOAc (3×100 mL)
washThe combined organic layers were washed with brine
dry with materialdried with sodium sulfate (Na2SO4)
concentrationconcentrated in vacuo
customto afford an orange oil
customRecrystallization from EtOAc/hexanes

Sources & evidence

ORD record: ord-5c240bf597994783a2c0937fb427487f
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07642270B2

Reaction notes

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