Diisopropylethylamine → 1-Tert-butyl 3-methyl 4-(2-cyano-4-nitrophenyl)piperazine-1,3-dicarboxylate

HRID 1186215Notes

Reaction equation

HRID 1186215 reaction equation
[N:1]1([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5][NH:4][CH:3]([C:7]([O:9][CH3:10])=[O:8])[CH2:2]1.C(N(CC)C(C)C)(C)C.F[C:28]1[CH:35]=[CH:34][C:33]([N+:36]([O-:38])=[O:37])=[CH:32][C:29]=1[C:30]#[N:31]>O1CCCC1>[C:30]([C:29]1[CH:32]=[C:33]([N+:36]([O-:38])=[O:37])[CH:34]=[CH:35][C:28]=1[N:4]1[CH2:5][CH2:6][N:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:2][CH:3]1[C:7]([O:9][CH3:10])=[O:8])#[N:31]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5194172-Fluoro-5-nitrobenzonitrileHCID 27568191-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate

Product 1

HCID 670010711-Tert-butyl 3-methyl 4-(2-cyano-4-nitrophenyl)piperazine-1,3-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-tert-butyl 3-methyl piperazine-1,3-dicarboxylate (80 g, 328 mmol) and N,N-diisopropylethylamine (192 mL, 741 mmol) in 300 mL of dry tetrahydrofuran was added 2-fluoro-5-nitrobenzonitrile (36 g, 219 mmol) at room temperature. The reaction mixture was heated to reflux for 36 hours. The reaction was concentrated and the resulting residue was purified by silica gel chromatography (30% ethyl acetate in hexane) to give the title compound: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.41 (s, 9H), 3.01-3.15 (m, 1H), 3.29-3.36 (m, 1H), 3.34-3.36 (m, 1H), 3.48-3.55 (m, 1H), 3.66 (s, 3H), 3.72-3.76 (m, 1H), 4.43-7.48 (m, 1H), 4.96-4.98 (m, 1H), 7.30 (d, J=9.1 Hz, 1H), 8.32 (dd, J=9.5, 2.8 Hz, 1H), 8.55 (d, J=2.8 Hz, 1H); MS (DCI/NH3) m/z 391 (M+H)+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 36 hours
  3. concentrationThe reaction was concentrated
  4. customthe resulting residue was purified by silica gel chromatography (30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ea020b89fbb645298eb5924a88644b51
Source dataset
uspto-grants-2014_03
Patent number
US08673896B2

Reaction notes

Loading…