Water → 1-[2-Ethyl-5-(ethyloxy)-4-nitrophenyl]-4-[2-(methylsulfonyl)ethyl]piperazine

HRID 419607Notes

Reaction equation

HRID 419607 reaction equation
[CH2:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([O:12][CH2:13][CH3:14])=[CH:5][C:4]=1F)[CH3:2].C([O-])([O-])=O.[K+].[K+].Cl.[CH3:23][S:24]([CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)(=[O:26])=[O:25].O>CS(C)=O>[CH2:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([O:12][CH2:13][CH3:14])=[CH:5][C:4]=1[N:32]1[CH2:31][CH2:30][N:29]([CH2:28][CH2:27][S:24]([CH3:23])(=[O:25])=[O:26])[CH2:34][CH2:33]1)[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 594528781-Ethoxy-4-ethyl-5-fluoro-2-nitrobenzeneHCID 666496671-[2-(Methylsulfonyl)ethyl]piperazine hydrochloride

Product 1

HCID 594526601-[2-Ethyl-5-(ethyloxy)-4-nitrophenyl]-4-[2-(methylsulfonyl)ethyl]piperazineYield 69.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

1-Ethyl-2-fluoro-4-(ethyloxy)-5-nitrobenzene (Example 208, step A) (0.50 g, 2.3 mmol) was dissolved in DMSO (15 mL). K2CO3 (0.97 g, 7.0 mmol) and 1-[2-(methylsulfonyl)ethyl]piperazine hydrochloride (Example 148, step B) (1.0 g, 4.7 mmol) were added and the reaction mixture was heated to 80° C. and allowed to stir over the weekend. The mixture was then heated to 120° C. for 4 h. The mixture was cooled to rt then poured into H2O and extracted with DCM. The combined organics were dried with MgSO4, filtered, and concentrated in vacuo. The crude product was purified on a 40 g ISCO column (EtOAc to 10% MeOH in EtOAc). The desired fractions were combined and the solvent removed in vacuo to give the title compound of Step A (0.63 g, 1.6 mmol, 66%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.78 (s, 1H), 6.56 (s, 1H), 4.12 (q, J=7.0 Hz, 2H), 3.23-3.12 (m, 2H), 3.03 (s, 3H), 3.00-2.91 (m, 6H), 2.72-2.62 (m, 4H), 2.57 (q, J=7.5 Hz, 2H), 2.22 (s, 3H), 1.44 (t, J=7.0 Hz, 3H), 1.22 (t, J=7.5 Hz, 3H). MS (M+H, ES+) 386.

Workup

  1. temperatureThe mixture was then heated to 120° C. for 4 h
  2. temperatureThe mixture was cooled to rt
  3. extractionextracted with DCM
  4. dry with materialThe combined organics were dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified on a 40 g ISCO column (EtOAc to 10% MeOH in EtOAc)
  8. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-4ec0a0b3224441c4abb3d08fbca8086b
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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