4-(4-Fluorobenzoyl)butyric acid

108-55-4

462-06-6

149437-76-3

4-(4-Fluorobenzoyl)butyric acid was synthesized as follows: 250 g of anhydrous AlCl3 (1.87 mol) and 300 mL of fluorobenzene (307.5 g; 3.2 mol) were added to a 2 L three-necked round-bottomed flask, and the mixture was cooled to 5 °C in an ice bath. A turbid suspension of 100 g of glutaric anhydride (0.86 mol) dissolved in 400 mL of fluorobenzene (4.3 mol) was slowly added through the addition funnel over 45 min, keeping the reaction temperature below 12 °C. The reaction mixture was gradually warmed to room temperature and stirred for 90 min and the completion of the reaction was monitored by NMR. The reaction mixture was cooled to 0 to 5 °C and 700 mL of a cold aqueous solution of 1N HCl was carefully added to quench unreacted AlCl3, keeping the temperature below 20 °C initially and not exceeding 40 °C later. The mixture was poured into 2 L of a 1:1 mixture of water and ice (v/w) to precipitate the crude product, and the white suspension was filtered and washed well with water. The white solid was dissolved in 3 L of 5% NaHCO3 saturated aqueous solution, heated in a steam bath for 1 h and then filtered through a diatomaceous earth pad while hot. The filtrate was cooled to room temperature, adjusted to pH 1 by adding about 320 mL of concentrated HCl drop by drop, the product crystallized and stirred in an ice bath for 30 minutes. Filtered, the wet filter cake was washed with ice-cold water and dried under vacuum at 50 °C for 16 h. 143.2 g of 4-(4-fluorobenzoyl)butyric acid was obtained with a melting point of 141 to 142 °C and a yield of 79.3%.