Water → 5-Aminoindole

The ethyl ester of 5-nitroindole-2-carboxylic acid (0.300 g, 1.28 mmol) was dissolved in anhydrous DMF (6 mL) and NaH (0.078 g, 60%, 1.92 mmol) was added. The reaction was stirred at RT for 20 min, then MeI (160 μL, 2.56 mmol) was added and stirring was continued for 3 h. The reaction was quenched with the addition of aqueous NaHCO3 (˜1%) while stirring vigorously. The brown solid formed (0.096 g) was filtered and dried in air overnight. The N-methyl nitro derivative (196 mg, 0.79 mmol) was then dissolved in DMF (4 mL), H2O (400 μL) and SnCl22H2O (888 mg, 3.95 mmol) were added, and the mixture was stirred at 60° C. for 3 h. The mixture was then partitioned between 10% aqueous NaHCO3 and EtOAc and stirred vigorously. The aqueous layer was re-extracted with EtOAc and the combined EtOAc layers were washed with brine, dried over anhydrous MgSO4 and concentrated to dryness. The residue was purified by flash column chromatography, using 1:1 ration EtOAc/hexane as the eluent, to obtain the pure 5-aminoindole derivative (118 mg) of example 27.

1. stirringstirring
2. waitwas continued for 3 h
3. customThe reaction was quenched with the addition of aqueous NaHCO3 (˜1%)
4. stirringwhile stirring vigorously
5. customThe brown solid formed (0.096 g)
6. filtrationwas filtered
7. customdried in air overnight
8. stirringthe mixture was stirred at 60° C. for 3 h
9. customThe mixture was then partitioned between 10% aqueous NaHCO3 and EtOAc
10. stirringstirred vigorously
11. extractionThe aqueous layer was re-extracted with EtOAc
12. washthe combined EtOAc layers were washed with brine
13. dry with materialdried over anhydrous MgSO4
14. concentrationconcentrated to dryness
15. customThe residue was purified by flash column chromatography

ORD record

ord-ff357ee2c80945cb82ea5b6cc47383a7

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07888363B2