Sulfuric Acid → alpha-Methyl-4'-(methoxy)[1,1'-biphenyl]-4-acetic acid, ethyl ester

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Reaction Conditions

Reaction Steps

The known starting material, 4'-methoxy-4-biphenylacetic acid (J. Chem. Soc. 1959, 557) is first converted to its ethyl ester by Fisher esterification with ethanol and concentrated sulfuric acid. To a solution of 4'-methoxy-4-biphenylacetic acid, ethyl ester (30.0 g, 0.110 mol) in tetrahydrofuran (400 mL) at -78° C. is added slowly, 2.01M lithium diisopropylamide (63 mL). The mixture is stirred for 30 minutes and then methyl iodide (30 mL) is added rapidly. The reaction mixture is warmed to 0° C. for 30 minutes, then at room temperature for 3 hours. The mixture is poured into water (2 L) and is extracted with ethyl acetate (3×1 L). The combined ethyl acetate extract is washed with 1N HCl (1 L), water (1 L) and brine (1 L), dried over MgSO4 and is concentrated under reduced pressure to give 48 g of crude yellow oil. Purification of the product by column chromatography (12% ethyl acetate in hexane) gives 22.0 g (69.6%) of crystalline material, m.p. 52°-54° C.

Provenance & Evidence