Cesium carbonate → Tert-butyl 4-(3-fluoro-4-nitrophenyl)piperazine-1-carboxylate

HRID 1503837Notes

Reaction equation

HRID 1503837 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([F:11])[CH:3]=1.[N:12]1([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[F:11][C:4]1[CH:3]=[C:2]([N:15]2[CH2:14][CH2:13][N:12]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17][CH2:16]2)[CH:7]=[CH:6][C:5]=1[N+:8]([O-:10])=[O:9]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 27833624-Bromo-2-fluoro-1-nitrobenzene

Product 1

HCID 66738172Tert-butyl 4-(3-fluoro-4-nitrophenyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4-bromo-2-fluoro-1-nitrobenzene (5 g, 23 mmol), tert-butyl piperazine-1-carboxylate (4.24 g, 23 mmol), palladium diacetate (0.51 g, 2.3 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (2.13 g, 3.4 mmol) and cesium carbonate (14.8 g, 45 mmol) in toluene (120 mL) was heated under nitrogen at 60° C. for 20 hours. After cooling to ambient temperature, the mixture was concentrated and the residue was diluted with dichloromethane (300 mL) and washed with water. The combined organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (200-300 mesh) eluting with 3/1 petroleum ether/ethyl acetate to give the title compound. MS: 348 (M+Na+).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe mixture was concentrated
  3. additionthe residue was diluted with dichloromethane (300 mL)
  4. washwashed with water
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography on silica gel (200-300 mesh)
  10. washeluting with 3/1 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-00247088b5204658aeb726e825d46038
Source dataset
uspto-grants-2015_12
Patent number
US09212192B2

Reaction notes

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