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

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.

1. customthe temperature below 10 ° C.
2. stirringthe reaction mixture stirred at room temperature overnight
3. extractionextracted with ethyl acetate (3x)
4. washThe organic extracts were washed with aqueous sodium thiosulfate, 5% sodium bicarbonate solution and water
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. customsolvent evaporated
8. customThe crude residue was purified by flash chromatography over silica gel eluting with ethyl acetate:hexane (1:9)

ORD record

ord-44ddd455f4d843d484d2cb73f0fb1618

Source dataset

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06593335B1