Chlorotrimethylsilane → 2-(Bromomethyl)-7-chloroquinoline

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (3.6 ml, 24.86 mmol) in dry tetrahydrofuran (25.0 ml) at −20° C. under nitrogen was treated with a 2.5 M solution of n-butyllithium in hexane (10.0 ml, 24.86 mmol). This lithium diisopropylamide solution was stirred below −10° C. for 30 min and 7-chloroquinaldine (4.0 g, 22.6 mmol) was added in portions. The resulting dark red solution was stirred at −10° C., increasing to 0° C. for 1 h, cooled to −30° C. and treated with chlorotrimethylsilane (4.4 ml, 33.92 mol) dropwise to return a golden yellow solution. After stirring below −20° C. for 2 h a solution of bromine (1.2 ml, 22.6 mmol) in tetrahydrofuran (25.0 ml) was added dropwise over a 30 min period maintaining an addition temperature of below −20° C. at all times. The mixture was stirred below −20° C. for 1 h, quenched with water (300 ml), extracted into ethyl acetate (3×100 ml), the combined organic extracts were washed with saturated ammonium chloride solution (2×200 ml), dried (Na2SO4) and evaporation of the solvent afforded a brown oily solid. Column chromatography (ethyl acetate-light petroleum (b.p. 40-60° C.), 1:4) gave the title compound (3.62 g, 76%) as a yellow solid. Crystallised from light petroleum (b.p. 40-60° C.) as white crystals, m.p. 108-112° C. (lit. m.p. 112° C. (dec.)). vmax (nujol)/cm−1 1593.5, 1559.5. δH (270 MHz) 4.68 (2H, s, CH2Br); 7.50 (1H, dd, 6-H, Jo=8.6, Jm=2.0 Hz); 7.56 (1H, d, 3-H, Jo=8.3 Hz); 7.74 (1H, d, 5-H, Jo=8.9 Hz); 8.06 (1H, d, 8-H, Jm=2.0 Hz); 8.14 (1H, d, 4-H, Jo=8.6 Hz). δc(67.8 MHz) 34.0 (CH2Br), 121.4 (3-C), 125.6 (4a-C), 135.9 (8a-C), 137.1 (4-C), 158.0 (2-C). Remaining signals fall in the narrow range 128.0-128.3 ppm.

Provenance & Evidence