Diisopropylethylamine → 3-Fluoro-4-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)nitrobenzene

HRID 1108585Notes

Reaction equation

HRID 1108585 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][NH:8][CH2:7][C:6]1=[O:11].C(N(CC)C(C)C)(C)C.[F:21][C:22]1[CH:23]=[C:24]([N+:29]([O-:31])=[O:30])[CH:25]=[CH:26][C:27]=1F.FC(F)(F)C(O)=O.C(N(CC)C(C)C)(C)C>C(#N)C>[F:21][C:22]1[CH:23]=[C:24]([N+:29]([O-:31])=[O:30])[CH:25]=[CH:26][C:27]=1[N:8]1[CH2:9][CH2:10][N:5]([CH2:4][CH2:3][O:2][CH3:1])[C:6](=[O:11])[CH2:7]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 12593398N,N-diisopropylethylamine trifluoroacetateHCID 187839041-(2-Methoxyethyl)piperazin-2-one

Product 1

HCID 187839133-Fluoro-4-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)nitrobenzene

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-(2-Methoxyethyl)-2-oxopiperazine (4TFA salt, 13.5 g) was dissolved in acetonitrile (200 ml), and N,N-diisopropylethylamine (22.6 ml) followed by 3,4-difluoronitrobenzene (2.2 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-{2-methoxyethyl}-3-oxopiperazin-1-yl)nitrobenzene as a solid (4.07 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
  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-0793201206914d67a7c39c99a9472194
Source dataset
uspto-grants-2000_05
Patent number
US06069145

Reaction notes

Loading…