Propionic Acid → beta-Oxo-delta-phenyl-benzene pentanoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence