Ethanol → Ethyl 3-oxo-3-(pyridin-2-yl)propanoate

HRID 751258Notes

Reaction equation

HRID 751258 reaction equation
[O-]CC.[Na+].C(O)C.[C:8]([O:11][CH2:12][CH3:13])(=[O:10])[CH3:9].C([O:16][C:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)=O)C>C1(C)C=CC=CC=1>[CH2:12]([O:11][C:8](=[O:10])[CH2:9][C:17](=[O:16])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)[CH3:13]

Participants

6

Reactant 4

HCID 702EthanolHCID 8857Ethyl AcetateHCID 17307Ethyl 2-pyridinecarboxylateHCID 2723922Sodium ethoxide

Product 1

HCID 2736461Ethyl 3-oxo-3-(pyridin-2-yl)propanoateYield 91%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
90 °C

Procedure

Stir a mixture of sodium ethoxide (360 g, 5.29 mol, 2 eq), toluene (4 L), ethanol (18 mL, 0.265 mol, 0.1 eq) and ethyl acetate (1.04 L, 10.58 mol, 4 eq) in a 22 L flask equipped with a reflux condenser, nitrogen inlet and mechanical stirrer. Stir for 1 h as the mixture warms to 26° C. Add pyridine-2-carboxylic acid ethyl ester (Fluka; 400 g, 2.65 mol, 1 eq) and heat the mixture to reflux (90° C.) for 18 h. Cool the mixture to room temperature. Dilute with toluene (8 L), wash with water (6 L), and separate the layers. Acidify the aqueous layer to pH 5 with glacial acetic acid. Extract with ethyl acetate (2×4 L), dry the combined organic layers (sodium sulfate), filter and concentrate in vacuo to yield the subtitled compound (466 g, 91% yield) as a dark oil in 93% purity by HPLC analysis. MS ES+ m/e 194 (M+1).

Workup

  1. customequipped with a reflux condenser, nitrogen inlet and mechanical stirrer
  2. stirringStir for 1 h as the mixture
  3. customwarms to 26° C
  4. temperatureCool the mixture to room temperature
  5. washwash with water (6 L)
  6. customseparate the layers
  7. extractionExtract with ethyl acetate (2×4 L)
  8. dry with materialdry the combined organic layers (sodium sulfate)
  9. filtrationfilter
  10. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-9e8b84bfaf2245269adeef3d4acec98e
Source dataset
uspto-grants-2008_07
Patent number
US07405299B2

Reaction notes

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