1,2-Difluoro-4-nitrobenzene → Racemic-1-(2-fluoro-4-nitrophenyl)-trans-2,5-dimethylpiperazine

HRID 1011247Notes

Reaction equation

HRID 1011247 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][C@H:5]([CH3:8])[CH2:4][NH:3]1.F[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][C:11]=1[F:19]>C(#N)C>[F:19][C:11]1[CH:12]=[C:13]([N+:16]([O-:18])=[O:17])[CH:14]=[CH:15][C:10]=1[N:3]1[CH2:4][C@@H:5]([CH3:8])[NH:6][CH2:7][C@@H:2]1[CH3:1]

Participants

4

Reactant 2

HCID 1230531,2-Difluoro-4-nitrobenzeneHCID 2206722,5-Dimethylpiperazine, trans-

Product 1

HCID 57664344Racemic-1-(2-fluoro-4-nitrophenyl)-trans-2,5-dimethylpiperazineYield 40.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

trans-2,5-Dimethylpiperazine (4.81 g, 42.1 mmol) and 1,2-difluoro-4-nitrobenzene (10.00 g, 62.9 mmol) are dissolved in 60 mL of dry acetonitrile and refluxed for 3 h, upon which a yellow precipitate forms on the bottom of the flask. The crude reaction mixture is concentrated in vacuo and the residue is chromatographed (silica gel, 10% MeOH in CH2Cl2) to give 4.32 g (17.0 mmol, 40%) of racemic-1-(2-fluoro-4-nitrophenyl)-trans-2,5-dimethylpiperazine as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 1.01 (d, J=6.0 Hz, 3H), 1.09 (d, J=6.3 Hz, 3H), 2.45 (dd, J=11.5, 9.0 Hz, 1H), 2.72 (dd, J=12.1, 9.0 Hz, 1H), 3.05-3.12 (m, 1H), 3.15 (dd, J=12.1, 3.3 Hz, 1H), 3.26 (dd, 2H), 7.12 (t, J=8.5 Hz, 1H), 7.91 (dd, J=11.2, 2.4 Hz, 1H), 7.95-8.01 (m, 1H). LCMS-ESI (m/z): calcd for C12H16FN3O2, 253.1; [M+H]+ found, 254.4.

Workup

  1. temperaturerefluxed for 3 h, upon which a yellow precipitate forms on the bottom of the flask
  2. customThe crude reaction mixture
  3. concentrationis concentrated in vacuo
  4. customthe residue is chromatographed (silica gel, 10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-3659a48f4e6941639f77674eb6673395
Source dataset
uspto-grants-2011_07
Patent number
US07977352B2

Reaction notes

Loading…