Sulfuric Acid → 2-(5-Trifluoromethyl-1H-indol-3-YL)acetic acid

Temperature

90 °C

A mixture of 4-trifluoromethylphenylhydrazine (5 g), 4,4-dimethoxybutyric acid methyl ester (6 g) and 10% aqueous sulfuric acid (20 ml) was stirred for 6 hours under a nitrogen atmosphere at 90° C. The reaction mixture was allowed to cool, water was added, and then extraction was performed with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. A 2 N sodium hydroxide aqueous solution (10 ml) and methanol (10 ml) were added to the obtained residue, and the mixture was heated to reflux for one hour. Water was added to the reaction mixture which was then rendered acidic with concentrated aqueous hydrochloric acid, extracted with ethyl acetate, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography using a mixed solvent of dichloromethane, methanol, and acetic acid to obtain 0.11 g of the title compound as a colorless powder (1.5% yield).

1. temperatureto cool
2. extractionextraction
3. dry with materialThe organic layer was dried over sodium sulfate
4. concentrationconcentrated under reduced pressure
5. additionA 2 N sodium hydroxide aqueous solution (10 ml) and methanol (10 ml) were added to the obtained residue
6. temperaturethe mixture was heated
7. temperatureto reflux for one hour
8. additionWater was added to the reaction mixture which
9. extractionrendered acidic with concentrated aqueous hydrochloric acid, extracted with ethyl acetate
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated under reduced pressure
12. customThe obtained residue was purified by silica gel column chromatography

ORD record

ord-b44fc9d7a79a4cdc92c9d8b3d0ab477e

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06887890B2