Potassium Carbonate → 6-Hydroxy-2-methyl-1-benzofuran-3-carboxylic acid

Temperature

0 °C

To a slurry of aluminum trichloride (20.0 g, 150 mmol) in dichloromethane (200 mL) is added oxalyl chloride (13.0 mL, 150 mmol) and the mixture is stirred at 0° C. for 30 minutes. A solution of acetic acid 2-methyl-benzofuran-6-yl ester (9.50 g; 49.9 mmol) in dichloromethane (50 mL) is added over 10 minutes. The ice-bath is removed and the reaction is stirred at room temperature for 2 hours. The reaction mixture is cooled to 0° C. and quenched with MeOH (50 mL). The mixture is concentrated to a residue, dissolved in methanol (250 mL), and treated with potassium carbonate (8.28 g, 59.9 mmol). The mixture is stirred at room temperature for 16 hours, filtered through a pad of celite, and concentrated. The residue is diluted with water (100 mL) and extracted with EtOAc (250 mL×2). The combined organic layers are dried over Na2SO4, filtered, and concentrated. The crude product is purified by flash chromatography (eluted with 25% EtOAc/Hexanes), and the appropriate fractions are concentrated. The material is dried in vacuo to afford 6-hydroxy-2-methyl-benzofuran-3-carboxylic acid (9.56 g, 93%). ES/MS m/e 207.0 (M+1); 205.0 (M−1).

1. customThe ice-bath is removed
2. stirringthe reaction is stirred at room temperature for 2 hours
3. temperatureThe reaction mixture is cooled to 0° C.
4. customquenched with MeOH (50 mL)
5. concentrationThe mixture is concentrated to a residue
6. dissolutiondissolved in methanol (250 mL)
7. stirringThe mixture is stirred at room temperature for 16 hours
8. filtrationfiltered through a pad of celite
9. concentrationconcentrated
10. additionThe residue is diluted with water (100 mL)
11. extractionextracted with EtOAc (250 mL×2)
12. dry with materialThe combined organic layers are dried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated
15. customThe crude product is purified by flash chromatography (eluted with 25% EtOAc/Hexanes)
16. concentrationthe appropriate fractions are concentrated
17. customThe material is dried in vacuo

ORD record

ord-56418295301649d5b86ba2e958379af3

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07846960B2