N,N-Dimethylaniline → 3-Bromo-5-fluorophenol

Participants

Reaction Steps

To a solution of 1-bromo-3-fluoro-5-benzyloxybenzene (110.0 g, 0.39 mol; see step (i) above) and N,N-dimethylaniline (474.0 g, 3.92 mol) in anhydrous CH2Cl2 (1.0 L) at 0° C. was added aluminium chloride (156.0 g, 1.17 mol). After 10 min, the ice bath was removed and the stirring was continued for 2 h. The reaction was quenched by the cautious addition of 3N HCl (600 mL). The layers were separated, and the aqueous layer was extracted with CH2Cl2 (2× 150 mL). The combined organic extracts were washed with 2N HCl (250 mL) and H2O (3× 250 mL). To the organic layer was added 15% KOH (500 mL), and the layers were separated. The organic layer was further extracted with 2 N KOH (2× 70 mL). The combined aqueous layers were washed with CH2Cl2 (3× 100 mL) and then acidified with 4N HCl. The aqueous layer was extracted with Et2O (3× 125 mL) then, the combined Et2O extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford the sub-title compound (69.0 g, 92%) as a brown oil that was used without further purification.

Provenance & Evidence