Carbon Dioxide → 6-fluoro-1H-indole-7-carboxylic Acid

Temperatur

15 °C

60 ml THF were cooled down to −60° C. under argon and 27 ml of a 1.6M n-BuLi solution (42.9 mmol) in hexane were added followed by 2.9 g of 6-fluoro-1H-indole (21 mmol) in 12 ml THF (addition over 25 min, temperature between −72 and −70° C.). After 5 min additional stirring at this temperature, a solution of 4.8 g of potassium tert-butylate (42.9 mmol) in 18 ml THF were added at the same temperature over 30 min. The reaction mixture was then stirred for 2 h at −72° C. and then treated with a large excess of solid CO2 over 1.5 h (temperature raised by 15° C.). To the brown/orange suspension, 40 ml of water were added, and after addition of diethylether the phases were separated, the aqueous phase extracted with 2× diethylether. Finally the aqueous phase was treated with conc HCl until pH 1 and extracted twice with diethylether. The combined organic phases were then washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo, and crystallized from diethylether/hexane, leading to 1.9 g 6-fluoro-1H-indole-7-carboxylic acid, as a light brown solid (51%). MS: 177.9 (M−H)−

1. stirringThe reaction mixture was then stirred for 2 h at −72° C.
2. customwere separated
3. extractionthe aqueous phase extracted with 2× diethylether
4. additionFinally the aqueous phase was treated with conc HCl until pH 1
5. extractionextracted twice with diethylether
6. washThe combined organic phases were then washed with brine
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customcrystallized from diethylether/hexane

ORD-Eintrag

ord-dac9d86e6ae147cc85e7fd1b5c0b2848

Quelldatensatz

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07259183B2