Sodium Sulfite → Methyl 4-Bromo-3-hydroxybenzoate

Participants

Reaction Conditions

Reaction Steps

To a suspension of methyl 4-amino-3-hydroxybenzoate 69 (21.7 g, 127 mmol) in water (115 mL) at 0° C. was added a solution of sodium nitrite (9.1 g, 127 mmol) in water (50 mL). The resultant mixture was stirred at 0° C. for 1 h. Meanwhile, copper sulfate pentahydrate (42.4 g, 169 mmol) was dissolved in water (135 mL) with heating and sodium bromide (26.4 g, 257 mmol) was added slowly with stirring. The resultant dark green solution was stirred for 5 min, and then was treated with a solution of sodium sulfite (11.3 g, 90 mmol) in water (40 mL). The resultant lime green slurry was stirred for 5 min, and then cooled by the addition of ice. The ice water was decanted off, carefully avoiding dryness. The residue was rinsed with water (3×) and the resultant white solid was dissolved in 115 mL concentrated HBr (115 mL). This acidic copper bromide solution was added to the diazonium salt suspension (see above) at 0° C. The resultant mixture was gradually heated up to 100° C., then stirred at this temperature for 1 h. Significant foaming was observed. After this time, the reaction mixture was cooled and brought to pH 4-5 by the addition of sodium carbonate. EtOAc was added and the mixture was filtered. The filtrate was extracted with EtOAc (3×). The organic layers were dried over Na2SO4 and filtered to give 70. 1H NMR (400 MHz CDCl3) δ: 3.91 (s, 3H), 5.81 (br s, 1H), 7.48 (dd, J=8.5 Hz, 1.4 Hz, 1H), 7.54 (d, J=8.5 Hz, 1H), 7.68 (s, 1H). MS (EI) m/z (M−H−) 229.

Provenance & Evidence