Toluene → Ethyl 3-(6-methylpyridin-2-yl)-3-oxopropanoate

HRID 751254

Reaction equation

HRID 751254 reaction equation
[O-]CC.[Na+].C1(C)C=CC=CC=1.[C:12]([O:15][CH2:16][CH3:17])(=[O:14])[CH3:13].C[O:19][C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[N:23]=1)=O>C(O)(=O)C>[CH2:16]([O:15][C:12](=[O:14])[CH2:13][C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[N:23]=1)=[O:19])[CH3:17]

Participants

6

Reactant 4

HCID 1140TolueneHCID 8857Ethyl AcetateHCID 73022Methyl 6-methylpyridine-2-carboxylateHCID 2723922Sodium ethoxide

Product 1

HCID 59710028Ethyl 3-(6-methylpyridin-2-yl)-3-oxopropanoateYield 112.6%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
92 °C

Procedure

Stir a mixture of sodium ethoxide (90 g, 1.32 mol, 2 eq), toluene (0.5 L, 5 vol), and ethyl acetate (0.2 L, 1.98 mol, 3 eq) in a 2 L flask equipped with reflux condenser, mechanical stirrer, and nitrogen inlet. After 1 h, add 6-methyl-pyridine-2-carboxylic acid methyl ester (Cheung, Y, Tetrahedron Lett. 1979, 40, 3809-10; 100 g, 0.66 mol). Heat the mixture at reflux (92° C.) for 20 h. Cool the mixture to room temperature and acidify with glacial acetic acid to pH 6. Wash the resulting gel with water (0.5 L). Separate the layers and extract the aqueous layer with toluene (1×0.5 L) Dry the combined organic layers (sodium sulfate), filter, and concentrate in vacuo to yield the subtitled product (154 g) as a dark oil in 86% purity by HPLC analysis. MS ES+ m/e 208 (M+1).

Workup

  1. customequipped
  2. temperaturewith reflux condenser, mechanical stirrer, and nitrogen inlet
  3. temperatureHeat the mixture
  4. temperatureCool the mixture to room temperature
  5. washWash the resulting gel with water (0.5 L)
  6. customSeparate the layers
  7. extractionextract the aqueous layer with toluene (1×0.5 L)
  8. dry with materialDry the combined organic layers (sodium sulfate)
  9. filtrationfilter
  10. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-9e7952648ad74ddc88db4efa9ed90fb9
Source dataset
uspto-grants-2008_07
Patent number
US07405299B2

Linked notes

Loading…