Water → 4-Bromoindole

Temperature

110 °C

2-Bromo-6-nitrotoluene (3.2 g, 15 mmol), N,N-dimethylformamide dimethyl acetal (5.4 g, 45 mmol) and pyrrolidine (1.1 g, 15 mmol) were combined in 30 mL of DMF and heated at 110° C. The reaction mixture was stirred at 110° C. for 2.5 hours and then water was added. The aqueous layer was extracted with Et2O and the combined organic layers were washed with water and brine, dried over MgSO4 and concentrated. The brown syrup was dissolved in 80% aqueous AcOH (80 mL) and heated to 75° C. Zn powder (8.5 g), 130 mmol) was then added portionwise over 1 hour and the temperature was raised to 85° C. for 2 hours. The reaction mixture was filtered and water was added. The aqueous layer was extracted with Et2O and the combined organic layers were washed with saturated aqueous sodium bicarbonate and water, dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 20% EtOAc in Hexanes to provide 2 g of the title compound as a greenish oil used as such.

1. extractionThe aqueous layer was extracted with Et2O
2. washthe combined organic layers were washed with water and brine
3. dry with materialdried over MgSO4
4. concentrationconcentrated
5. dissolutionThe brown syrup was dissolved in 80% aqueous AcOH (80 mL)
6. temperatureheated to 75° C
7. additionZn powder (8.5 g), 130 mmol) was then added portionwise over 1 hour
8. temperaturethe temperature was raised to 85° C. for 2 hours
9. filtrationThe reaction mixture was filtered
10. additionwater was added
11. extractionThe aqueous layer was extracted with Et2O
12. washthe combined organic layers were washed with saturated aqueous sodium bicarbonate and water
13. dry with materialdried over Na2SO4
14. concentrationconcentrated
15. customThe residue was purified by silica gel chromatography
16. washeluted with 20% EtOAc in Hexanes

ORD record

ord-2917bdfbbf12437884679241e6a7b19b

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07144913B2