Chlorosuccinimide → 4-Nitro-1,3-dihydro-2H-indol-2-one

Temperature

70 °C

A mixture of 4-nitroindole (12.2 g, 75.2 mmol) and N-chlorosuccinimide (6.07 g, 30.1 mmol) in CHCl3 (500 mL) was heated at reflux for 30 h, then concentrated to dryness under reduced pressure. The residue was dissolved in AcOH (200 mL) and the resulting solution was warmed to 70° C., then 85% H3PO4 (80 mL) was added over 2 min. The mixture was heated to reflux for 90 min then cooled on ice. The cooled mixture was adjusted to pH 6 by addition of 10 N NaOH (450 mL), followed by aqueous NaHCO3, keeping the temperature below 30° C. The mixture was extracted with EtOAc (3×1 L) and the combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was partially purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 0:100, and then triturated with MeOH to give the title compound. MS: m/z=179 (M+1).

1. temperaturewas heated
2. temperatureat reflux for 30 h
3. concentrationconcentrated to dryness under reduced pressure
4. dissolutionThe residue was dissolved in AcOH (200 mL)
5. addition85% H3PO4 (80 mL) was added over 2 min
6. temperatureThe mixture was heated
7. temperatureto reflux for 90 min
8. temperaturethen cooled on ice
9. additionThe cooled mixture was adjusted to pH 6 by addition of 10 N NaOH (450 mL)
10. customthe temperature below 30° C
11. extractionThe mixture was extracted with EtOAc (3×1 L)
12. dry with materialthe combined organic extracts were dried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customThe crude product was partially purified by silica gel chromatography
16. washeluting with a gradient of hexane
17. customEtOAc—100:0 to 0:100, and then triturated with MeOH

ORD record

ord-47e521fd49904a9ebaaab1c3b877685c

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143266B2