Diisopropylethylamine → 3-Fluoro-4-(4-ethyl-3-oxopiperazin-1-yl)nitrobenzene

HRID 1108577Notes

Reaction equation

HRID 1108577 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][NH:6][CH2:5][C:4]1=[O:9])[CH3:2].C(N(CC)C(C)C)(C)C.[F:19][C:20]1[CH:21]=[C:22]([N+:27]([O-:29])=[O:28])[CH:23]=[CH:24][C:25]=1F.FC(F)(F)C(O)=O.C(N(CC)C(C)C)(C)C>C(#N)C>[F:19][C:20]1[CH:21]=[C:22]([N+:27]([O-:29])=[O:28])[CH:23]=[CH:24][C:25]=1[N:6]1[CH2:7][CH2:8][N:3]([CH2:1][CH3:2])[C:4](=[O:9])[CH2:5]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 98773661-Ethylpiperazin-2-oneHCID 12593398N,N-diisopropylethylamine trifluoroacetate

Product 1

HCID 187839123-Fluoro-4-(4-ethyl-3-oxopiperazin-1-yl)nitrobenzene

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-Ethyl-2-oxopiperazine (3TFA salt, 10.5 g) was dissolved in acetonitrile (200 ml), and N,N-diisopropylethylamine (19.5 ml) followed by 3,4-difluoronitrobenzene (2.25 ml) were added. The mixture was heated to reflux for 18 hours. Solvent was evaporated, and the residue chromatographed on silica using as eluant a gradient increasing in polarity from 0 to 4% methanol in dichloromethane. Relevant fractions were combined and evaporated to give a solid containing some N,N-diisopropylethylamine trifluoroacetate. The solid was purified by dissolving in ethyl acetate and washing well with water. Evaporation of the organic layer gave 3-fluoro-4-(4-ethyl-3-oxopiperazin-1-yl)nitrobenzene as a solid (3.44 g).

Workup

  1. additionwere added
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 18 hours
  4. customSolvent was evaporated
  5. customthe residue chromatographed on silica using as eluant
  6. temperaturea gradient increasing in polarity from 0 to 4% methanol in dichloromethane
  7. customevaporated
  8. customto give a solid
  9. customThe solid was purified
  10. dissolutionby dissolving in ethyl acetate
  11. washwashing well with water
  12. customEvaporation of the organic layer

Sources & evidence

ORD record
ord-e6d6bb280fdc4ebf98f0251e68132f1e
Source dataset
uspto-grants-2000_05
Patent number
US06069145

Reaction notes

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