Acetic Acid → 4-Bromo-6-fluoro-1H-indole

Temperatur

100 °C

To a solution of 1-bromo-5-fluoro-2-methyl-3-nitrobenzene (4.69 g, 20 mmol) in 1,4-dioxane (25 mL) at RT was slowly added DMF dimethylacetal (13.3 mL) and pyrrolidine (1.7 mL). The solution was heated at 100° C. for 18 h, then concentrated in vacuo to give a dark residue. To the residue was added HOAc (30 mL) and iron powder (11 g, 200 mmol) then the mixture was heated to reflux for 1 h, cooled to RT, neutralized by addition of 50% aq. NaOH and extracted with EtOAc (2×200 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with an EtOAc/petroleum ether gradient (5 to 30% EtOAc) to afford 1.16 g (27%) of 4-bromo-6-fluoro-1H-indole (224)—as brown solid: MS (ESI) m/z=213.9 [M+1]+.

1. customat RT
2. concentrationconcentrated in vacuo
3. customto give a dark residue
4. temperaturethe mixture was heated
5. temperatureto reflux for 1 h
6. temperaturecooled to RT
7. extractionextracted with EtOAc (2×200 mL)
8. dry with materialThe combined organic extracts were dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified by SiO2 chromatography
12. washeluting with an EtOAc/petroleum ether gradient (5 to 30% EtOAc)

ORD-Eintrag

ord-952faae079564f3ab9268fba4e57f743

Quelldatensatz

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08637537B2