Chloroform → 7-Bromo-2-chloroquinoline

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Reaction Steps

To a -78° C. solution of 18 (890 mg, 3.0 mmol) in dry THF (20 ml) was slowly added MeLi/LiBr (1.5M in ether, 2.2 ml, 3.3 mmol). The solution was stirred 30 min. at -78° C. at which time Br2 (excess) was added dropwise. The solution was warmed to room temperature, quenched with water, and the mixture extracted with ether. The combined ether extracts were dried (MgSO4) and concentrated. The residue was taken up in CH2Cl2 and passed through a short silica gel pad. The appropriate fractions were concentrated to afford a material which was immediately diluted with CHCl3 (20 ml). To this solution was added excess CH3CO2OH (32% solution in dilute HOAc) and the mixture was stirred overnight. The mixture was then poured into saturated NaHCO3 (aq) and extracted with ether. The combined ether extracts were dried (MgSO4) and concentrated to a tan solid to which was added excess POCl3 at 0° C. The mixture was warmed to 60° C., stirred for 15 min., and then cooled to room temperature. 1M NaOH was added and the mixture was extracted with ether. The combined ether extracts were dried (MgSO4) and concentrated to a residue which was purified by HPLC (Whatman Partisil 10 column, 90:10 CHCl3 :EtOAc) to afford 7-Bromo-2-chloroquinoline 19 (70 mg, 10% from 18). 1H NMR d (ppm): 7.4 d (CH arom), 7.7 s (2 CH arom), 8.2 d (CH arom), 8.3 s (CH arom).

Provenance & Evidence