3-(3,4-DIMETHYLPHENYL)PROPIONIC ACID

102-46-5

105-53-3

25173-76-6

Step 1) Synthesis of 3-(3,4-dimethylphenyl)propionic acid: 10.0 g of sodium metal was added batchwise to 70.0 mL of diethyl malonate dissolved in 400 mL of anhydrous ethanol. The reaction mixture was stirred at 0 °C for 30 min; 66.5 g of 3,4-dimethylbenzyl chloride was then added slowly and dropwise. The reaction mixture was continued to be stirred at room temperature for 1 hour, followed by reflux heating for 4 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure. The residue was dissolved in ether and the organic phase was washed with water. After concentrating the organic phase under reduced pressure, it was mixed with 500 mL of water and 170 g KOH; the mixture was heated at reflux for 24 hours. The reaction solution was concentrated under reduced pressure to half the original volume and 200 mL of 98% sulfuric acid was slowly added. The resulting solution was heated at reflux for 24 h. After cooling, the solution was extracted twice with 300 mL of ethyl acetate. The organic phases were combined, the solvent was removed by distillation under reduced pressure and the residue was recrystallized from boiling hexane to give 42.1 g of the title compound as a white solid (yield: 55%). Melting point: 82 °C. 1H-NMR (300 MHz, CDCl3) δ 2.22 (s, 3H, CH3), 2.24 (s, 3H, CH3), 2.66 (t, J = 8 Hz, 2H, ArCH2), 2.89 (t, J = 8 Hz, 2H, CH2CO), 6.93-7.70 (m, 3H, ArH).