Cesium carbonate → Ethyl ({4-[(2-(ethyloxy)-1-{6-[4-(trifluoromethyl)phenyl]-2-pyridinyl}ethyl)thio]-2-methylphenyl}oxy)acetate

HRID 1391800Notes

Reaction equation

HRID 1391800 reaction equation
[Cl-].CC1C=C(C)C=C(C)C=1[N+]1C=CN(C2C(C)=CC(C)=CC=2C)C=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[C:32]1[N:37]=[C:36]([CH:38]([S:43][C:44]2[CH:49]=[CH:48][C:47]([O:50][CH2:51][C:52]([O:54][CH2:55][CH3:56])=[O:53])=[C:46]([CH3:57])[CH:45]=2)[CH2:39][O:40][CH2:41][CH3:42])[CH:35]=[CH:34][CH:33]=1.[F:58][C:59]([F:72])([F:71])[C:60]1[CH:65]=[CH:64][C:63](B2OCCO2)=[CH:62][CH:61]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:41]([O:40][CH2:39][CH:38]([S:43][C:44]1[CH:49]=[CH:48][C:47]([O:50][CH2:51][C:52]([O:54][CH2:55][CH3:56])=[O:53])=[C:46]([CH3:57])[CH:45]=1)[C:36]1[CH:35]=[CH:34][CH:33]=[C:32]([C:63]2[CH:64]=[CH:65][C:60]([C:59]([F:72])([F:71])[F:58])=[CH:61][CH:62]=2)[N:37]=1)[CH3:42]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27342111,3-Bis(2,4,6-trimethylphenyl)imidazolium chlorideHCID 205838462-[4-(Trifluoromethyl)phenyl]-1,3,2-dioxaborolaneHCID 58629945Ethyl [(4-{[1-(6-bromo-2-pyridinyl)-2-(ethyloxy)ethyl]thio}-2-methylphenyl)oxy]acetate

Product 1

HCID 58629824Ethyl ({4-[(2-(ethyloxy)-1-{6-[4-(trifluoromethyl)phenyl]-2-pyridinyl}ethyl)thio]-2-methylphenyl}oxy)acetateYield 24.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

To a mixture of palladium (II) acetate (6 mg, 0.027 mmol), 1,3-bis(2,4,6-trimethylphenyl)imidazoliumchloride (9 mg, 0.026 mmol) and Cs2CO3 (266 mg, 0.816 mmol) in 1,4-dioxane (1 mL) was added ethyl [(4-{[1-(6-bromo-2-pyridinyl)-2-(ethyloxy)ethyl]thio}-2-methylphenyl)oxy]acetate (125 mg, 0.275 mmol) in 1,4-dioxane (1.75 mL) and the resulting mixture stirred under nitrogen at ambient temperature for 10 min. 2-[4-(Trifluoromethyl)phenyl]-1,3,2-dioxaborolane (69 mg, 0.300 mmol) was then added and the resulting mixture heated to 85° C. and kept at this temperature for 16 h. The reaction mixture was then reduced and the residue partitioned between EtOAc (15 mL) and saturated aqueous NH4Cl (15 mL) and the layers separated. The aqueous layer was then re-extracted with EtOAc (15 mL) and the combined organic layers washed with brine (50 mL) dried (MgSO4) and filtered. The mixture was then reduced under vacuum and the resulting residue purified by SPE (silica, 10 g cartridge), eluting with cyclohexane:EtOAc (gradient 50:1 to 3:1). Further purification by mass directed autoprep HPLC afforded the title compound as an oil (35 mg).

Workup

  1. temperaturethe resulting mixture heated to 85° C.
  2. waitkept at this temperature for 16 h
  3. customthe residue partitioned between EtOAc (15 mL) and saturated aqueous NH4Cl (15 mL)
  4. customthe layers separated
  5. extractionThe aqueous layer was then re-extracted with EtOAc (15 mL)
  6. washthe combined organic layers washed with brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe resulting residue purified by SPE (silica, 10 g cartridge)
  10. washeluting with cyclohexane
  11. customFurther purification by mass

Sources & evidence

ORD record
ord-fae6fd40381349d9a9307bb088923bb7
Source dataset
uspto-grants-2008_03
Patent number
US07338960B2

Reaction notes

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