Pyrrolidine → 6-Bromoindole

Temperature

110 °C

To a solution of 4-bromo-2-nitrotoluene (4.3 g., 20 mmol.) in DMF (40 mL.) was added DMF dimethylacetal (7.15 g., 60 mmol.) and pyrrolidine (1.4 g., 20 mmol.). The solution was heated to 110° C. for 4 hr. then cooled to rt. and diluted with ethyl ether. The mixture was washed 3×with water, dried with Na2SO4, filtered and the solvent evaporated. The residue was dissolved in 80% aqueous acetic acid (125 mL.) and heated to 75° C. Zinc dust (9.75 g., 150 mmol.) was added gradually over 20 min. The reaction mixture was heated to 85° C. for 2 hr. then cooled to ~35° C. and filtered to remove unreacted zinc. The filtrate was diluted with ethyl ether, washed 3×with water then with saturated aqueous NaHCO3. The solution was dried with Na2SO4, filtered and concentrated in vacuo to ~30 mL. then diluted with hexanes and filtered. The filtrate was concentrated to an off-white solid which was dissolved in hexane, filtered, and concentrated to give 1.65 g. of the title compound as a light green solid.

1. temperaturethen cooled to rt
2. washThe mixture was washed 3×with water
3. dry with materialdried with Na2SO4
4. filtrationfiltered
5. customthe solvent evaporated
6. dissolutionThe residue was dissolved in 80% aqueous acetic acid (125 mL.)
7. temperatureheated to 75° C
8. temperatureThe reaction mixture was heated to 85° C. for 2 hr
9. temperaturethen cooled to ~35° C.
10. filtrationfiltered
11. customto remove unreacted zinc
12. additionThe filtrate was diluted with ethyl ether
13. washwashed 3×with water
14. dry with materialThe solution was dried with Na2SO4
15. filtrationfiltered
16. concentrationconcentrated in vacuo to ~30 mL
17. additionthen diluted with hexanes
18. filtrationfiltered
19. concentrationThe filtrate was concentrated to an off-white solid which
20. dissolutionwas dissolved in hexane
21. filtrationfiltered
22. concentrationconcentrated
23. customto give 1.65 g

ORD record

ord-b13a6fff7926494bb805a1346308642e

Source dataset

uspto-grants-1994_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05310901