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

HRID 1269586Notes

Reaction equation

HRID 1269586 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:67]=[CH:66][C:56]([O:57][C:58]([CH3:65])([CH3:64])[C:59]([O:61][CH2:62][CH3:63])=[O:60])=[C:55]([CH3:68])[CH:54]=1)[CH2:48][CH2:49][CH3:50].Br[C:70]1[CH:75]=[CH:74][CH:73]=[C:72]([C:76]2[CH:81]=[CH:80][C:79]([C:82]([F:85])([F:84])[F:83])=[CH:78][CH:77]=2)[N:71]=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:67]=[CH:66][C:56]([O:57][C:58]([CH3:65])([CH3:64])[C:59]([O:61][CH2:62][CH3:63])=[O:60])=[C:55]([CH3:68])[CH:54]=1)[C:70]1[CH:75]=[CH:74][CH:73]=[C:72]([C:76]2[CH:81]=[CH:80][C:79]([C:82]([F:83])([F:85])[F:84])=[CH:78][CH:77]=2)[N:71]=1)[CH2:48][CH2:49][CH3:50]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 184483252-Bromo-6-(4-(trifluoromethyl)phenyl)pyridineHCID 18448412Ethyl 2-{4-[(butylamino)methyl]-2-methylphenoxy}-2-methylpropanoate

Product 1

HCID 18448411Ethyl 2-{4-[(butyl{6-[4-(trifluoromethyl)phenyl]pyridin-2-yl}amino)methyl]-2-methylphenoxy}-2-methylpropanoateYield 42.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Palladium (II) acetate (1.4 mg, 0.006 mmol) and (S)-2,2′-bis(diphenylphosphino)-1,1′-binapthyl (5.9 mg, 0.0095 mmol) in anhydrous toluene (0.32 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 ethyl 2-{4-[(butylamino)methyl]-2-methylphenoxy}-2-methylpropanoate (29 mg, 0.095 mmol), 2-bromo-6-[4-(trifluoromethyl)phenyl]pyridine (24 mg, 0.08 mmol) and caesium carbonate (36 mg, 0.11 mmol) were added. The vial was then sealed and heated at 80° C. for 18 h, then allowed to cool to room temperature the reaction mixture filtered and the solvent removed in vacuo. Purification by SPE (Silica, 10 g) eluting with 99:1 cyclohexane:EtOAc afforded the title compound as a colourless oil (18 mg).

Workup

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

Sources & evidence

ORD record
ord-29a313d2c79e4e6ab81cfa0fb3215033
Source dataset
uspto-grants-2007_04
Patent number
US07199239B2

Reaction notes

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