Chemical Properties
White Solid
Uses
An impurity in the synthesis of Aripiprazole (A771000). A degradation product in Aripiprazole tablets.
Synthesis
Example-1: Preparation of 7-(4-bromobutoxy)-3,4-dihydroquinolone [BBQ] was carried out as follows: in a 3-liter, three-necked, round-bottomed flask equipped with a mechanical stirrer, a condenser, and a thermometer, 100 grams of 3,4-dihydro-7-hydroxy-2(1H)-quinolone, 397.5 grams of 1,4-dibromobutane, 42.33 grams of potassium carbonate, and 300 ml of N,N-dimethylformamide. After mixing with stirring at room temperature (30-35 °C), the reaction mixture was heated to 40-45 °C and maintained at this temperature for 1 hour. Subsequently, a second batch of potassium carbonate (42.33 g) was added and the reaction was continued at 40-45 °C for 1 hour. Next, a third batch of potassium carbonate (42.33 g) was added and the reaction was continued at the same temperature for 4-5 hours. After completion of the reaction, the mixture was cooled to room temperature, poured into 1500 ml of water and stirred for 30 minutes. Extraction was carried out by adding 500 ml of chloroform and the organic layer was washed with water after layering. The extraction was repeated once more with 500 ml of chloroform. The organic phases were combined and washed with 10% sodium hydroxide solution and after separating the layers, the chloroform layer was washed with 1500 ml of water. Subsequently, the organic solvent was removed by vacuum distillation. To remove the trace solvent, solvent exchange was performed with 2 x 250 ml of cyclohexane. To the residue, 300 ml of cyclohexane was added, stirred for 3 hours and filtered, and the solid was washed with 200 ml of cyclohexane. Finally, the product was dried in a disk dryer at 65-70 °C for 10-12 hours until the weight loss was less than 1%. The product was obtained as 148 g in 80.95% yield and 86.09% HPLC purity.
References
[1] Asian Journal of Chemistry, 2011, vol. 23, # 4, p. 1655 - 1660
[2] Arzneimittel-Forschung/Drug Research, 2006, vol. 56, # 10, p. 673 - 677
[3] Patent: WO2008/1188, 2008, A2. Location in patent: Page/Page column 8-9
[4] Journal of Medicinal Chemistry, 1998, vol. 41, # 5, p. 658 - 667
[5] Patent: US2006/79689, 2006, A1. Location in patent: Page/Page column 11
