Dimethylformamide → HCID 22490569, compound

Temperature

80 °C

A mixture of 3-ethoxycarbonylamino-4-iodobenzotrifluoride (1.8 g), 2,5-dihydro-2,5-dimethoxyfuran (1.3 g), palladium acetate (60 mg), diisopropylethylamine (2.0 g), benzyltriethylammonium chloride (1.2 g) and DMF (15 ml) was stirred for 20 hours under a nitrogen atmosphere at 80° C. Water and ethyl acetate were added to the reaction mixture, the insoluble portion was filtered out with celite, and extraction was performed with ethyl acetate. The organic layer was collected and dried over sodium sulfate and then concentrated under reduced pressure. Dichloromethane (25 ml) and trifluoroacetic acid (1.5 ml) were added to the obtained residue, and the mixture was stirred at room temperature for 2 hours. Saturated sodium bicarbonate water was added to the reaction mixture and vigorously stirred therewith. The organic layer was collected and dried over sodium sulfate and then concentrated under reduced pressure. A (1-ethoxycarbonyl-6-trifluoromethyl-1H-indol-3-yl)acetic acid methyl ester component was purified from the obtained residue by silica gel column chromatography using a mixed solvent of hexane and ethyl acetate. A 2 N sodium hydroxide aqueous solution (1 ml) and methanol (1 ml) were added to the obtained (1-ethoxycarbonyl-6-trifluoromethyl-1H-indol-3-yl)acetic acid methyl ester, 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 and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure, to obtain 77 mg of the title compound as a colorless powder (5% yield).

1. filtrationthe insoluble portion was filtered out with celite, and extraction
2. customThe organic layer was collected
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated under reduced pressure
5. additionDichloromethane (25 ml) and trifluoroacetic acid (1.5 ml) were added to the obtained residue
6. stirringthe mixture was stirred at room temperature for 2 hours
7. additionSaturated sodium bicarbonate water was added to the reaction mixture
8. stirringvigorously stirred
9. customThe organic layer was collected
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated under reduced pressure
12. customA (1-ethoxycarbonyl-6-trifluoromethyl-1H-indol-3-yl)acetic acid methyl ester component was purified from the obtained residue by silica gel column chromatography
13. additionA 2 N sodium hydroxide aqueous solution (1 ml) and methanol (1 ml) were added to the obtained (1-ethoxycarbonyl-6-trifluoromethyl-1H-indol-3-yl)acetic acid methyl ester
14. temperaturethe mixture was heated
15. temperatureto reflux for one hour
16. additionWater was added to the reaction mixture, which
17. extractionrendered acidic with concentrated aqueous hydrochloric acid and extracted with ethyl acetate
18. dry with materialThe organic layer was dried over sodium sulfate
19. concentrationconcentrated under reduced pressure

ORD record

ord-f41ddd91282a47c896cba5ec3733147b

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06887890B2