Cesium carbonate → HCID 89692897, compound

HRID 1481882Notes

Reaction equation

HRID 1481882 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1.Br[C:48]1[CH:53]=[C:52]([F:54])[CH:51]=[CH:50][C:49]=1[CH3:55].[C:56]([O:60][C:61]([N:63]1[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]1)=[O:62])([CH3:59])([CH3:58])[CH3:57]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:56]([O:60][C:61]([N:63]1[CH2:68][CH2:67][N:66]([C:48]2[CH:53]=[C:52]([F:54])[CH:51]=[CH:50][C:49]=2[CH3:55])[CH2:65][CH2:64]1)=[O:62])([CH3:59])([CH3:57])[CH3:58]

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 740162-Bromo-4-fluorotolueneHCID 143452tert-Butyl piperazine-1-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl

Product 1

HCID 89692897HCID 89692897, compoundYield 55.4%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

In a 50 ml round bottom flask equipped with a magnetic stir bar and fitted with a nitrogen inlet, the XPhos (210.80 mg, 0.44 mmol) and the cesium carbonate (1.80 g, 5.52 mmol) were combined dry. This mixture was taken up in 1,4-dioxane (10.00 ml, 116.91 mmol) and the 2-bromo-4-fluoro-1-methyl-benzene 16a (1.04 g, 5.53 mmol) was added followed by the piperazine-1-carboxylic acid tert-butyl ester 16b (514.80 mg, 2.76 mmol). The mixture was stirred together under vacuum at room temperature for 10 min and then the system was flushed with nitrogen. The palladium(II) acetate (62.10 mg, 0.28 mmol) was added to the reaction in one portion and the reaction was warmed to 100° C. and was allowed to stir under nitrogen overnight. The reaction was cooled to room temperature and filtered through Celite, washing with ethyl acetate. The collected product solution was then concentrated under reduced pressure and the product was purified from the resultant dark brown oil using silica gel column chromatography, eluting a gradient of 100% heptanes to 50% ethyl acetate in heptanes. 4-(5-fluoro-2-methyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester 16c (451.00 mg, 1.53 mmol) was isolated as an off-white solid. LCMS (m/e)=295 (M+H).

Workup

  1. customIn a 50 ml round bottom flask equipped with a magnetic stir bar
  2. customfitted with a nitrogen inlet
  3. customthe system was flushed with nitrogen
  4. temperaturethe reaction was warmed to 100° C.
  5. stirringto stir under nitrogen overnight
  6. temperatureThe reaction was cooled to room temperature
  7. filtrationfiltered through Celite
  8. washwashing with ethyl acetate
  9. concentrationThe collected product solution was then concentrated under reduced pressure
  10. customthe product was purified from the resultant dark brown oil
  11. washeluting a gradient of 100% heptanes to 50% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-2d85db9fb2b54fee8f9db9cbe9be3c10
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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