Synthesis
2-(4-Fluorophenyl)-1,1,3-trimethoxycarbonylpropane (6.7 g, 21.5 mmol) was used as starting material and dissolved in methanol (100 ml). To this solution, aqueous sodium hydroxide solution (3N, 23 ml, 69 mmol) was slowly added at room temperature. The reaction mixture was stirred for 12 hours. After completion of the reaction, most of the solvent was removed by concentration under reduced pressure. Subsequently, water (20 ml) and concentrated hydrochloric acid (10 ml) were added to the concentrate and the mixture was heated to reflux under ice bath cooling. After cooling, the reaction mixture was extracted with ethyl acetate. The organic phases were combined and washed sequentially with water and saturated sodium chloride solution and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product. The crude product was purified by crystallization from ethyl acetate and washed with hexane to give finally 3-(4-fluorophenyl)glutaric acid (4.5 g, 93% yield) with a melting point of 145-147 °C. 1H-NMR (DMSO-d6) δ: 2.48 (2H, dd, J = 15.8,8.8 Hz), 2.64 (2H, dd, J = 15.8,6.2 Hz). 3.20-3.56 (1H, m), 7.00-7.20 (2H, m), 7.22-7.40 (2H, m), 12.1 (2H, br s).
References
[1] Patent: EP1411052, 2004, A1. Location in patent: Page 53-54
[2] Tetrahedron Asymmetry, 2001, vol. 12, # 3, p. 419 - 426
