Synthesis
The general procedure for the synthesis of 5-acetyl-8-benzyloxy-1H-quinolin-2-one from 5-acetyl-8-hydroxyquinolin-2(1H)-one (8.13 g, 40 mmol, 1.0 eq.) and benzyl bromide (7.52 g, 44 mmol, 1.10 eq.) was as follows: crude 5-acetyl-8-hydroxyquinolin-2(1H)-one was added to acetone (64 mL) containing N ,N-diisopropylethylamine (6.46 g, 50 mmol, 1.25 equiv) in acetone (64 mL). After heating the suspension to reflux temperature, water (8.2 mL) was added. Benzyl bromide was slowly added dropwise and the reaction mixture was kept at reflux temperature for 6-7 hours until the feedstock was completely consumed. Upon completion of the reaction, water (20 mL) was added at 58°C and the mixture was cooled to 20-25°C. The product was collected by filtration and washed sequentially with acetone/water (1:1, 2 x 8.5 mL) and water (4 x 8 mL). The crude product was dried under vacuum at 60 °C overnight to give 10.77 g (91.7% yield) of 5-acetyl-8-benzyloxy-1H-quinolin-2-one with 99.5% purity of the crude product. The product can be further purified by recrystallization from acetone/water system.
References
[1] Patent: WO2004/87668, 2004, A1. Location in patent: Page 29
[2] Patent: WO2005/123684, 2005, A2. Location in patent: Page/Page column 34
[3] Patent: US2004/224982, 2004, A1. Location in patent: Page 10
[4] Patent: US2004/242622, 2004, A1. Location in patent: Page 29
[5] Patent: US2004/167167, 2004, A1. Location in patent: Page/Page column 32
