Synthesis
1c) Synthesis of methyl 6-bromo-2-quinolinecarboxylate
A mixture of 6-bromo-2-quinolinecarboxylic acid (331 g, multiple batches, 1.31 mol) and methanesulfonic acid (22 mL, 33 g, 0.34 mol) in methanol (2 L) was refluxed for 6 hours. Upon completion of the reaction, the reaction mixture was neutralized with an aqueous solution of sodium bicarbonate (29 g, 0.34 mol) (350 mL). The resulting suspension was slowly cooled to 20 °C and stirred continuously overnight. The solid product was collected by filtration and the filter cake was washed with water (1 L). The solid product was dried in a vacuum oven at 50 °C for 3 days to give methyl 6-bromo-2-quinolinecarboxylate (294 g, 85% yield).
1H NMR (400 MHz, DMSO-d6) δ 8.52 (d, J = 9 Hz, 1H), 8.40 (d, J = 2 Hz, 1H), 8.14 (d, J = 9 Hz, 1H), 8.08 (d, J = 9 Hz, 1H), 7.97 (m, 1H), 3.93 (s, 3H).
ES-LCMS m/z 267 (M + H)+.
References
[1] Patent: US2008/96921, 2008, A1. Location in patent: Page/Page column 32
[2] Tetrahedron, 2014, vol. 70, # 42, p. 7686 - 7690
[3] Patent: WO2011/127643, 2011, A1. Location in patent: Page/Page column 38
