Sulfuric Acid → 5-Bromo-4-fluoro-2-iodobenzaldehyde

Participants

Reaction Steps

To a solution of Example 115A (1.0 g, 4.0 mmol) in 1: 1 ethanol-water (50 mL), was added iron-powder (0.6 g) then 6 N hydrochloric acid (1 mL). The reaction mixture was heated to reflux overnight, cooled, neutralized with I N sodium hydroxide, filtered, and the filtrate extracted with ethyl acetate (3x). The organic extracts were dried over magnesium sulfate, filtered and solvent evaporated to provide 0.68 g of 5-bromo-4-fluoro-2-aminobenzaldehyde. To a solution of 2-amino-5-bromo-4-fluorobenzaldehyde (0.68 g, 3.1 mmol) in water (10 mL) at 0 ° C. was added sulfuric acid (2 mL) then slowly a solution of sodium nitrite (0.23 g, 3.4 mmol) in water (10 mL) keeping the temperature below 10 ° C.. After stirring at this temperature for 1 hour this suspension was added to a solution of potassium iodide (0.50 g, 3.1 mmol) in water (20 mL), the reaction mixture stirred at room temperature overnight, extracted with ethyl acetate (3x). The organic extracts were washed with aqueous sodium thiosulfate, 5% sodium bicarbonate solution and water, then dried over magnesium sulfate, filtered and solvent evaporated. The crude residue was purified by flash chromatography over silica gel eluting with ethyl acetate:hexane (1:9) to provide 0.16 g of the title compound as a tan solid.

Provenance & Evidence