Reaktion #1285215

Reaktionsgleichung

propionic acid

malonate

3,3-diphenylpropionic acid

3,3-diphenylpropionic acid

1,1'-carbonyldiimidazole

ethyl potassium malonate

Triethylamine

magnesium chloride

→

desired product

Ausbeute 51.0%

β-oxo-δ-phenyl-benzene pentanoic acid ethyl ester

Ausbeute 51.0%

Lösungsmittel

THF

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter 3 hours
2. 2
   Temperaturto gradually warm to room temperature
3. 3
   workup.STIRRINGstir for 4 hours
4. 4
   workup.STIRRINGthis reaction mixture was stirred at room temperature for 16 hours
5. 5
   SonstigeThis pale yellow heterogeneous reaction mixture was then carefully quenched with a solution of 200 g sodium bisulfate in 700 mL water
6. 6
   workup.ADDITIONEthyl acetate (3L) was then added to the yellow homogeneous solution
7. 7
   Sonstigethe layers were separated
8. 8
   Waschenthe organic layer was washed with 1L 5% NAOH solution and 1L saturated NaCl solution
9. 9
   workup.ADDITIONThe organic layer was then diluted with 1.5L hexane
10. 10
    Trocknendried (MgSO4)
11. 11
    Einengenconcentrated in vacuo (30° C.)
12. 12
    Sonstigeto give a yellow oil
13. 13
    SonstigePurification by flash chromatography (silica gel, 15% EtOAc/hexane)

Vorschrift

To a cooled solution (0° C.) of 3,3-diphenylpropionic acid (50.0 g, 0.220 mol) in 300 mL THF, 1,1'-carbonyldiimidazole (43.0 g, 0.265 mol) was added portionwise (exotherm to 10° C.) and stirred at 0° C. for 3 hours. After 3 hours, in a separate flask (equipped with an overhead stirrer), magnesium chloride (40.0 g, 0.418 mol) was added to a cooled solution (0° C.) of ethyl potassium malonate (60.0 g, 0.352 mol) in 400 mL acetonitrile (exotherm to 30° C.). Triethylamine (48.9 g, 0.484 mol) was then added and this mixture and the 3,3-diphenylpropionic acid mixture were separately allowed to gradually warm to room temperature and stir for 4 hours. The propionic acid mixture was then added dropwise to the malonate mixture (exotherm to 30° C.) and this reaction mixture was stirred at room temperature for 16 hours. This pale yellow heterogeneous reaction mixture was then carefully quenched with a solution of 200 g sodium bisulfate in 700 mL water. Ethyl acetate (3L) was then added to the yellow homogeneous solution, the layers were separated, and the organic layer was washed with 1L 5% NAOH solution and 1L saturated NaCl solution. The organic layer was then diluted with 1.5L hexane, dried (MgSO4), and concentrated in vacuo (30° C.) to give a yellow oil. Purification by flash chromatography (silica gel, 15% EtOAc/hexane) yielded 33.2 g (0.112 mol, 51%) of the desired product.

Quelle