Cesium fluoride → Ethyl 3-[3-(3-methoxypropoxy)-4-pyridin-3-ylphenyl]propanoate

HRID 1690630Notes

Reaction equation

HRID 1690630 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]([CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:10]=[CH:11][C:12]=1OS(C(F)(F)F)(=O)=O.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30](B(O)O)[CH:29]=1.[F-].[Cs+]>C(COC)OC.C(O)C>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]([CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:10]=[CH:11][C:12]=1[C:30]1[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 27343783-Pyridinylboronic acidHCID 86633298Ethyl 3-[3-(3-methoxypropoxy)-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl]propanoate

Product 1

HCID 66906575Ethyl 3-[3-(3-methoxypropoxy)-4-pyridin-3-ylphenyl]propanoateYield 55%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Ethyl 3-[3-(3-methoxypropoxy)-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl]propanoate (1.0 g, 2.4 mmol) was dissolved in dimethoxyethane (15 mL) and ethanol (1.5 mL). Pyridin-3-ylboronic acid (0.33 g, 2.65 mmol) was added and argon was bubbled in the mixture for 15 minutes. Cesium fluoride (0.8 g, 5.3 mmol) and tetrakistriphenylphosphine palladium (0.14 g, 0.1 mmol) were added and the mixture was brought to reflux under an argon atmosphere for 4 hours. After cooling to room temperature, solvents were evaporated under reduced pressure and the residue was dissolved in ethyl acetate/water (15 mL/15 mL). The organic layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate, 9/1) to yield 0.45 g (55%) of the desired product as a yellow oil.

Workup

  1. customargon was bubbled in the mixture for 15 minutes
  2. temperatureto reflux under an argon atmosphere for 4 hours
  3. customsolvents were evaporated under reduced pressure
  4. dissolutionthe residue was dissolved in ethyl acetate/water (15 mL/15 mL)
  5. washThe organic layer was washed with saturated aqueous sodium bicarbonate and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate, 9/1)

Sources & evidence

ORD record
ord-692ef49d16d34d2aac088c56d88b3c7d
Source dataset
uspto-grants-2012_04
Patent number
US08153647B2

Reaction notes

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