1,2-Difluoro-4-nitrobenzene → tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate

HRID 2384892Notes

Reaction equation

HRID 2384892 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1F.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]>C(#N)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([C:7]2[CH:6]=[CH:5][C:4]([N+:9]([O-:11])=[O:10])=[CH:3][C:2]=2[F:1])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

4

Reactant 2

HCID 1230531,2-Difluoro-4-nitrobenzeneHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 16203508tert-Butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylateYield 72%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Dissolve 3,4-difluoronitrobenzene (2.0 g, 12.6 mmol) in acetonitrile (35 mL) and add piperazine-1-carboxylic acid tert-butyl ester (4.7 g, 25.2 mmol). Heat the mixture at reflux for 16 h. Cool the mixture to room temperature and concentrate in vacuo. Partition the residue between dichloromethane (75 mL) and water (75 mL), separate the organic portion and extract the aqueous portion with dichloromethane (2×25 mL). Combine the organics and dry (Na2SO4), filter, and concentrate in vacuo to give 2.83 g (72%) of the title compound. MS/ES m/z 270.2 [M-tertBu+H]+.

Workup

  1. temperatureHeat the mixture
  2. temperatureat reflux for 16 h
  3. concentrationconcentrate in vacuo
  4. customPartition the residue between dichloromethane (75 mL) and water (75 mL)
  5. customseparate the organic portion
  6. extractionextract the aqueous portion with dichloromethane (2×25 mL)
  7. dry with materialCombine the organics and dry (Na2SO4)
  8. filtrationfilter
  9. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-aece0d14e7554f13a9a442c7fc8a56aa
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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