Dimethyl Sulfoxide → 1-[2-Fluoro-3-(methyloxy)-4-nitrophenyl]-4-(1-methylethyl)piperazine

HRID 1014241Notes

Reaction equation

F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[C:3]=1[F:13].CS(C)=O.[CH:18]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)([CH3:20])[CH3:19].C(=O)([O-])[O-].[K+].[K+]>O>[F:13][C:3]1[C:4]([O:11][CH3:12])=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[N:24]1[CH2:25][CH2:26][N:21]([CH:18]([CH3:20])[CH3:19])[CH2:22][CH2:23]1

Participants

Conditions

Temperature: 70 °C

Procedure

A pressure flask was charged with 1,2-difluoro-3-(methyloxy)-4-nitrobenzene (3.5 g, 18.5 mmol), dimethylsulfoxide (100 mL), isopropyl piperazine (5.41 mL, 22.2 mmol) and potassium carbonate (5.1 g, 37.04 mmol). The resulting slurry was warmed to 70° C. and stirred overnight. The next morning, the orange solution was poured into water and extracted with diethyl ether. The organic layer was dried over sodium sulfate, taken to a residue under reduced pressure, and purified via chromatography on SiO2 (0 to 10% MeOH/CH2CL2 with 0.2% NH3) to afford 1-[2-fluoro-3-(methyloxy)-4-nitrophenyl]-4-(1-methylethyl)piperazine as a yellow solid (5.7 g, quant. yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.10 (d, J=6.60 Hz, 6 H), 2.71 (s, 4 H), 2.76 (s, 1 H), 3.29 (s, 4 H), 4.03 (s, 3 H), 6.64 (dd, J=9.53, 8.07 Hz, 1 H), 7.70 (dd, J=9.35, 2.02 Hz, 1 H).

Workup

extractionextracted with diethyl ether
dry with materialThe organic layer was dried over sodium sulfate
custompurified via chromatography on SiO2 (0 to 10% MeOH/CH2CL2 with 0.2% NH3)

Sources & evidence

ORD record: ord-85fcc0f487044b899694a9f57c4c5540
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07981903B2

Reaction notes

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