Synthesis
To a 6N hydrochloric acid (300 mL) solution of o-bromoaniline (100 g, 0.58 mol) was slowly added trans-2-butenal (81 g, 1.1 mol) at room temperature. The reaction mixture was heated to 100 °C and stirred overnight. Upon completion of the reaction, the mixture was cooled to room temperature, alkalized to pH 8-9 with ammonium hydroxide solution and subsequently extracted with ether (3 × 100 mL). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with petroleum ether/ethyl acetate (12:1 to 10:1, v/v) as eluent to afford 8-bromo-2-methylquinoline as a white solid (59 g, 54% yield). Mass spectrometry (ESI) analysis: calculated value for C10H8BrN was 222.1; measured value was 223 [M + H]+.
References
[1] Patent: WO2010/101949, 2010, A1. Location in patent: Page/Page column 116; 117
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 10, p. 4066 - 4084
[3] Patent: WO2009/80675, 2009, A1. Location in patent: Page/Page column 14
[4] Arkivoc, 2015, vol. 2015, # 3, p. 38 - 51
