Acetic Acid → Ethyl 3-Oxo-3-phenyl-2-(pyridin-3-yl)propanoate

HRID 1430600Notes

Reaction equation

HRID 1430600 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:2]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:23](Cl)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CC(O)=O>C1COCC1.O>[O:30]=[C:23]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:7]([C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 7412Benzoyl chlorideHCID 96490Ethyl 3-pyridylacetateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 67422224Ethyl 3-Oxo-3-phenyl-2-(pyridin-3-yl)propanoateYield 55.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled solution (−78° C.) of ethyl 2-(pyridin-3-yl)acetate (1.842 mL, 12.11 mmol) in THF (12.2 mL) was added LiHMDS (12.11 mL, 12.11 mmol) and the mixture was stirred 15 min. A solution of benzoyl chloride (1.474 mL, 12.71 mmol) in THF (24.4 mL) was added slowly and the mixture was warmed to room temperature and stirred for 12 h. The reaction was quenched with AcOH (1.386 mL, 24.21 mmol), diluted with H2O (50 mL), and extracted with EtOAc (3×75 mL). The combined extracts were washed with brine, dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a clear oil (1.82 g). LCMS m/z=270.2 [M+H]+.

Workup

  1. stirringstirred for 12 h
  2. extractionextracted with EtOAc (3×75 mL)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3ecaada707dd48c29155950d3a588c7c
Source dataset
uspto-grants-2015_01
Patent number
US08940891B2

Reaction notes

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