[Synthesis]
Synthesis of 4-(4-fluorophenyl)butyric acid: 4-(4-fluorophenyl)-4-oxobutanoic acid (0.98 g, 5 mmol) and 85% KOH (0.79 g, 12 mmol) were added to a round bottomed flask fitted with a Dean-Stark apparatus and a reflux condenser and suspended in diethylene glycol (10 mL). 50% hydrazine monohydrate (1.20 g, 12 mmol) was added slowly at room temperature and the reaction mixture was subsequently heated to 120-130 °C and maintained for 2 hours. After about 45 min, the reaction mixture became homogeneous. after 2 h, the temperature was increased to 180-200 °C and stirring was continued for 3 h. Residual hydrazine and water were removed by means of a Dean-Stark water separator. After completion of the reaction, it was cooled to room temperature, diluted with H2O (10 mL) and poured into 2.5N aqueous HCl (20 mL). The organic product was extracted with EtOAc (3 x 15 mL), the organic phases were combined, washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (30-50% EtOAc/hexane) afforded the target product 4-(4-fluorophenyl)butanoic acid as a clear viscous oil (0.32 g, 35%).1H NMR (500 MHz, CDCl3): δ 11.50 (br, 1H), 7.16 (m, 2H), 7.00 (m, 2H), 2.67 (t, J = 7.6 Hz, 2H), 2.40 (t, J = 7.4 Hz, 2H), 1.97 (quin, J = 7.5 Hz, 2H).13C NMR (125 MHz, CDCl3): δ 180.16, 161.34 (d, J = 243.4 Hz), 136.74, 129.76 (d, J = 7.3 Hz), 115.09 (d, J = 7.3 Hz), 115.09 (d, J = 7.3 Hz), 115.09 (d, J = 7.3 Hz), 115.09 (d, J = 7.3 Hz), 115.09 (d, J = 7.3 Hz) 115.09 (d, J = 20.9 Hz), 34.09, 33.20, 26.24. |
[References]
[1] Patent: US5872118, 1999, A
[2] Patent: US6124284, 2000, A
[3] Patent: US5719186, 1998, A
[4] Archiv der Pharmazie, 1998, vol. 331, # 12, p. 395 - 404
[5] Patent: WO2015/134973, 2015, A1. Location in patent: Page/Page column 98 |