Quinoline, 4-(bromomethyl)-2-methyl- synthesis

Yield: 94%

Reaction Conditions:

with N-Bromosuccinimide;triphenylphosphine in tetrahydrofuran at 0 - 20;

Steps:

1
4-(bromomethyl)-2-methylquinoline. To a solution of (2-methyl-quinolin-4-yl)-methanol (200 mg, 1.15 mmol) in THF (8 ml) at 0° C. was added NBS (431 mg, 2.42 mmol) and triphenylphosphine (605 mg, 2.31 mmol). The reaction mixture was allowed to warm to room temperature and stirred reaction overnight. The reaction mixture was quenched with sat NaHCO₃ and extracted with ethyl acetate. The organic portions were dried over MgSO₄, filtered and concentrated. Column chromatography on silica gel (10-30% ethyl acetate/hexanes) afforded intermediate 1 (258 mg, 1.09 mmol, 94%). ¹H NMR (400 MHz, CDCl₃) δ ppm 7.95-8.18 (m, 2H), 7.65-7.81 (m, 1H), 7.43-7.66 (m, 1H), 7.32 (s, 1H), 4.82 (s, 2H), 2.73 (s, 3H).

References:

Bristol-Myers Squibb Company US2009/18163, 2009, A1 Location in patent:Page/Page column 20