Cesium carbonate → Methyl {4-[(butyl{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino)methyl]-2-methylphenoxy}acetate

HRID 1269587Notes

Reaction equation

HRID 1269587 reaction equation
C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH2:47]([NH:51][CH2:52][C:53]1[CH:64]=[CH:63][C:56]([O:57][CH2:58][C:59]([O:61][CH3:62])=[O:60])=[C:55]([CH3:65])[CH:54]=1)[CH2:48][CH2:49][CH3:50].Br[C:67]1[CH:72]=[CH:71][CH:70]=[C:69]([C:73]2[CH:78]=[CH:77][C:76]([C:79]([F:82])([F:81])[F:80])=[CH:75][CH:74]=2)[N:68]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:47]([N:51]([CH2:52][C:53]1[CH:64]=[CH:63][C:56]([O:57][CH2:58][C:59]([O:61][CH3:62])=[O:60])=[C:55]([CH3:65])[CH:54]=1)[C:67]1[CH:72]=[CH:71][CH:70]=[C:69]([C:73]2[CH:78]=[CH:77][C:76]([C:79]([F:80])([F:82])[F:81])=[CH:75][CH:74]=2)[N:68]=1)[CH2:48][CH2:49][CH3:50]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 184483252-Bromo-6-(4-(trifluoromethyl)phenyl)pyridineHCID 58622898Methyl {4-[(butylamino)methyl]-2-methylphenoxy}acetate

Product 1

HCID 58622857Methyl {4-[(butyl{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino)methyl]-2-methylphenoxy}acetateYield 34.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Palladium (II) acetate (5.4 mg, 0.024 mmol) and (S)-2,2′-bis(diphenylphosphino)-1,1′-binapthyl (22 mg, 0.036 mmol) in anhydrous toluene (1.2 mL) were stirred together at 70° C. in a sealed reactivial for 30 minutes. The vial was then allowed to attain room temperature before the methyl {4-[(butylamino)methyl]-2-methylphenoxy}acetate (96 mg, 0.36 mmol), 2-bromo-6-[4-(trifluoromethyl)phenyl]pyridine (90.6 mg, 0.3 mmol) and caesium carbonate (137 mg, 0.42 mmol) were added. The vial was then sealed and heated at 80° C. for 18 h. The reaction mixture was allowed to cool to room temperature, the reaction mixture filtered and the solvent removed in vacuo. Purification by SPE (Silica, 10 g) eluting 99:1–50:1 cyclohexane:EtOAc afforded the title compound as a colourless oil (50 mg).

Workup

  1. additionwere added
  2. customThe vial was then sealed
  3. temperatureto cool to room temperature
  4. filtrationthe reaction mixture filtered
  5. customthe solvent removed in vacuo
  6. customPurification by SPE (Silica, 10 g)
  7. washeluting 99:1–50:1 cyclohexane

Sources & evidence

ORD record
ord-48fcca34f05546e092e3571a1f626f67
Source dataset
uspto-grants-2007_04
Patent number
US07199239B2

Reaction notes

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