Reaction Steps
To a solution of methyl 8-acetylquinoline-2-carboxylate (1.98 g, 8.64 mmol) in DCM (25 mL) at 0° C. was added TEA (1.56 mL, 11.23 mmol) followed by TBSOTf (1.66 mL, 9.50 mmol). The reaction mixture was stirred at 0° C. for 50 min. The mixture was then partitioned between saturated NaHCO3 and DCM. The organic layer was separated, and the aq. layer was extracted with DCM (2×). The combined organic layers were then dried over anhydrous MgSO4, filtered, and concentrated in vacuo to give methyl 8-(1-((tert-butyldimethylsilyl)oxy)vinyl)quinoline-2-carboxylate as a brown oil: 1H NMR (400 MHz, CDCl3) δ ppm 8.29 (d, J=8.4 Hz, 1H), 8.18 (d, J=8.4 Hz, 1H), 8.12 (dd, J=7.3, 1.3 Hz, 1H), 7.80 (dd, J=8.1, 1.3 Hz, 1H), 7.62 (t, J=7.7 Hz, 1H), 6.12 (s, 1H), 4.99 (s, 1H), 4.05 (s, 3H), 1.01 (s, 9H), 0.28 (s, 6H). m/z (ESI, +ve ion) 344.0 (M+H)+. This oil was taken up in THF (10 mL), treated with water (2.5 mL, 138 mmol) and NBS (1.61 g, 9.07 mmol), and stirred at RT for 20 min. The reaction mixture was then partitioned between water and Et2O, and the organic layer was separated and sequentially washed with saturated NaHCO3, water, and brine, then dried over MgSO4, filtered, and concentrated in vacuo to give methyl 8-(2-bromoacetyl)quinoline-2-carboxylate as a greenish-brown solid. This material was used without purification in the subsequent step assuming the theoretical yield: 1H NMR (400 MHz, CDCl3) δ ppm 8.40 (d, J=8.6 Hz, 1H), 8.30 (d, J=7.0 Hz, 1H), 8.26 (d, J=8.6 Hz, 1H), 8.09 (d, J=8.2 Hz, 1H), 7.76 (t, J=7.6 Hz, 1H), 5.32 (br. s., 2H), 4.08 (s, 3H). m/z (ESI, +ve ion) 308.0/310.1 (M+H)+.
