Sulfuric Acid → 4-Bromo-5-formyl-benzo[1,3]dioxole-2-carboxylic acid methyl ester

To a mixture of 2-bromo-3,4-dihydroxy-benzaldehyde (2.17 g, 10.0 mmol) and K2CO3 (5.56 g, 40.2 mmol) in n-propanol (25 mL) was added dibromoacetic acid (2.18, 10.0 mmol) and the mixture was heated at reflux temperature for 24 h. After cooling to room temperature, another portion of dibromoacetic acid (1.75 g, 8.0 mmol) was added. The mixture was stirred at reflux for 46 h. n-Propanol was evaporated and water (30 mL) was added. The resulting aqueous solution was acidified to pH 2 by adding 1 N HCl and extracted with ethyl acetate (3×100 mL). The combined organic layers were dried (MgSO4) and evaporated in vacuo to afford crude 4-bromo-5-formyl-benzo[1,3]dioxole-2-carboxylic acid (1.34 g) as a brownish solid. This crude product was dissolved in anhydrous methanol (50 mL) and conc. H2SO4 (5 mL) was added drop by drop. The resulting mixture was refluxed overnight and cooled to room temperature. Water (50 mL) was added and the resulting aqueous solution was extracted with ethyl acetate (100 mL×3). The combined organic layers were dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (ethyl acetate:hexane=5:95) to furnish 4-bromo-5-formyl-benzo[1,3]dioxole-2-carboxylic acid methyl ester as a white solid.

1. temperaturethe mixture was heated
2. temperatureat reflux temperature for 24 h
3. customwas evaporated
4. additionwater (30 mL) was added
5. additionby adding 1 N HCl
6. extractionextracted with ethyl acetate (3×100 mL)
7. dry with materialThe combined organic layers were dried (MgSO4)
8. customevaporated in vacuo
9. customto afford crude 4-bromo-5-formyl-benzo[1,3]dioxole-2-carboxylic acid (1.34 g) as a brownish solid
10. temperatureThe resulting mixture was refluxed overnight
11. temperaturecooled to room temperature
12. extractionthe resulting aqueous solution was extracted with ethyl acetate (100 mL×3)
13. dry with materialThe combined organic layers were dried (MgSO4)
14. customevaporated in vacuo
15. customThe residue was purified by flash column chromatography (ethyl acetate:hexane=5:95)

ORD record

ord-671dd3dd86974b028e656e7c964c4937

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06936719B2