Uses
8-Bromo-5-fluoroquinoline is used as a novel binder in the synthesis of 5HT1A, and also acts as a receptor antagonist and agonist. This drug has excellent efficacy for central nervous system disorders, such as cognitive impairment, anxiety disorders, depression, and sexual dysfunction.
Synthesis
2-Bromo-5-fluoroaniline (100 g, 1.0 eq.), 4-nitrophenol (40 g, 0.54 eq.) and glycerol (97 g, 2.0 eq.) were slowly added to pre-mixed sulfuric acid (267 mL) and water (114 mL) at 140-150 °C and the reaction lasted for 1.5 h. The reaction was carried out by HPLC. At the beginning of the reaction, the relative area percentage of 4-nitrophenol was shown to be 37.8% by HPLC analysis. The content of 4-nitrophenol decreased to 4.7% after the addition of 50% of the feedstock and further decreased to 5.0% after the addition of all the feedstock. Upon completion of the reaction, 8-bromo-5-fluoroquinoline was obtained after post-treatment in 87.5% yield with 0.29% total impurities. In addition, reducing the amount of 4-nitrophenol to 0.46 equivalents (34 g) was also successful in synthesizing the target intermediate in acceptable yield.
References
[1] Patent: US2007/27160, 2007, A1. Location in patent: Page/Page column 66
[2] Patent: US2007/299083, 2007, A1. Location in patent: Page/Page column 9
[3] Patent: WO2007/146072, 2007, A2. Location in patent: Page/Page column 73-74
[4] Patent: WO2008/67390, 2008, A2. Location in patent: Page/Page column 101-102
[5] Patent: US2007/27160, 2007, A1. Location in patent: Page/Page column 63-65
