Hydrochloric Acid → 4-(4-Fluoro-3-methylphenyl)-4-oxobutanoic acid

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Reaction Conditions

Reaction Steps

To an oven dried three neck flask was added Mg turnings (355 mg, 14.6 mg-at.) catalytic amount of iodine, and 20 mL THF. To the resulting mixture was added dropwise 4-bromo-1-fluoro-2-methyl-benzene (1.0 g, 0.005 mol) with heating to ˜62° C. After completing the addition of the aryl bromide, the mixture was stirred for an additional 30 min at 62° C. The THF solution of the prepared aryl magnesium bromide was cooled to −70° C. and succinic anhydride (1.0 g, 0.01 mmol) added as a solution in 10 mL THF. The mixture was vigorously stirred with warming to rt over 3 h and then hydrolyzed by the addition of 30 mL of 1M HCl. The resulting mixture was extracted with ethyl acetate (2×20 mL). The combined organic layers were extracted with 5% aqueous K2CO3 (3×10 mL) and the combined aqueous layers acidified with 1M HCl to pH3. A milky colloidal suspension was extracted with ethyl acetate (3×30 mL) and the combined organic layers washed with brine (2×20 mL). The solvent was evaporated under reduced pressure and the crude product used directly in the next step without further purification.

Provenance & Evidence