Acetone → 6-Bromo-4-phenyl-3-isocoumarincarboxylic acid

To a solution of 4-bromo-2-benzoylbenzoic acid (57.6 g) in acetone (500 ml) was added potassium carbonate (26.1 g), and the mixture was stirred at room temperature for 10 min. to allow precipitation of potassium salt. Then diethyl bromomalonate (54.2 g) and DMF (25 ml) were added, and the mixture was stirred at room temperature for 20 hrs. The reaction mixture was concentrated, and ethyl acetate (200 ml) and water (200 ml) were added to the residue. The mixture was stirred at room temperature for 30 min. After separating the organic layer, the layer was washed with water and brine, dried over sodium sulfate and concentrated. A mixed solution of acetic acid (200 ml) and conc. hydrochloric acid (200 ml) was added to the obtained residue, and the mixture was stirred at 120° C. for 15 hrs. After cooling, the reaction mixture was concentrated, and the residue was dissolved in ethyl acetate, washed with water and brine, dried over sodium sulfate and concentrated. The obtained residue was crystallized from isopropyl ether and collected by filtration to give the title compound (53 g) as colorless crystals.

1. customprecipitation of potassium salt
2. additionThen diethyl bromomalonate (54.2 g) and DMF (25 ml) were added
3. stirringthe mixture was stirred at room temperature for 20 hrs
4. concentrationThe reaction mixture was concentrated
5. additionethyl acetate (200 ml) and water (200 ml) were added to the residue
6. stirringThe mixture was stirred at room temperature for 30 min
7. customAfter separating the organic layer
8. washthe layer was washed with water and brine
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated
11. additionA mixed solution of acetic acid (200 ml) and conc. hydrochloric acid (200 ml) was added to the obtained residue
12. stirringthe mixture was stirred at 120° C. for 15 hrs
13. temperatureAfter cooling
14. concentrationthe reaction mixture was concentrated
15. dissolutionthe residue was dissolved in ethyl acetate
16. washwashed with water and brine
17. dry with materialdried over sodium sulfate
18. concentrationconcentrated
19. customThe obtained residue was crystallized from isopropyl ether
20. filtrationcollected by filtration

ORD record

ord-72ea7a8786e64b03a96dcd15df33eeda

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07402595B2