Aniline → 8-bromo-3-methyl-N-phenylquinolin-2-amine

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Reaction Conditions

Reaction Steps

NaH (60% w/w in mineral oil; 390 mg, 9.75 mmol) was added to a solution of aniline (0.888 mL, 9.75 mmol) in DMF (4.0 mL) at 0° C. and the resulting suspension was stirred at 0° C. for 2 min, then warmed to 25° C. and stirred for 5 min. 8-Bromo-2-chloro-3-methylquinoline (Example 104b; 529 mg, 2.062 mmol) was added as a solid, and the resulting solution was stirred at 25° C. for 1.5 h, then at 80° C. bath for 2.5 h. The mixture was cooled to 25° C. and partitioned between EtOAc (100 mL) and saturated aq. NH4Cl (80 mL). The organic layer was separated and the aq. layer was extracted with EtOAc (2×50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-40% EtOAc/hexanes) furnished 8-bromo-3-methyl-N-phenylquinolin-2-amine (182.0 mg, 0.581 mmol, 28% yield) as a brown oil: m/z (ESI, +ve) 313.1 (M+H)+.

Provenance & Evidence