Dichloromethane → 7-Bromo-4-methoxy-1H-indole

2-Bromo-5-methoxy-aniline (4.4 g, 21.8 mmol) was added dropwise to a solution of boron trichloride in methylene chloride (1.0 M, 24 mL, 24 mmol) cooled with ice water. The reaction mixture was warmed to room temperature, stirred for 30 min, and chloroacetonitrile (4.01 mL, 26.2 mmol) and aluminum chloride (4.01 g, 24.0 mmol) were added, followed by 1,2-dichloroethane (28.5 mL). The reaction mixture was heated to 70° C. to distill off methylene chloride, and then heated to reflux for 24 hrs. After cooling to 0–5° C., the mixture was treated with 2.5 M HCl (38.4 mL) carefully, and then heated to 80° C. for 1 h until all solids dissolved. The aqueous layer was separated, extracted with methylene chloride and the combined extracts washed with water and brine, dried (sodium sulfate) and evaporated to a yellow solid, which was used without further purification. The crude product was taken into dioxane (37 mL) and water (4.2 mL), and treated with sodium borohydride (0.91 g, 24.0 mmol) in portions. After stirring at room temperature for 30 min, all the starting material was consumed and the reaction mixture was then heated to reflux for 14 hrs. After cooling to room temperature, the mixture was treated with concentrated HCl, and extracted with ethyl acetate. The organic extract was washed with water and brine; dried (sodium sulfate), and concentrated. Column chromatography on silica gel (hexanes/ethyl acetate) gave 4-methoxyl-7-bromoindole (1.2 g, 24%). 1H NMR (400 MHz, CDCl3) 3.94 (s, 3H), 6.44 (d, J=8.21 Hz, 1H), 6.73 (m, 1H), 7.17 (t, J=2.74 Hz, 1H), 7.22˜7.26 (m, 1H), 8.32 (br, 1H); MS (ES, m/z): C9H8BrNO: 227.99 (M+(79Br)+1), 230.0(M+(81Br)+1).

1. temperatureThe reaction mixture was heated to 70° C.
2. distillationto distill off methylene chloride
3. temperatureheated
4. temperatureto reflux for 24 hrs
5. temperatureAfter cooling to 0–5° C.
6. additionthe mixture was treated with 2.5 M HCl (38.4 mL) carefully
7. temperatureheated to 80° C. for 1 h until all solids
8. dissolutiondissolved
9. customThe aqueous layer was separated
10. extractionextracted with methylene chloride
11. washthe combined extracts washed with water and brine
12. dry with materialdried (sodium sulfate)
13. customevaporated to a yellow solid, which
14. customwas used without further purification
15. stirringAfter stirring at room temperature for 30 min
16. customall the starting material was consumed
17. temperaturethe reaction mixture was then heated
18. temperatureto reflux for 14 hrs
19. temperatureAfter cooling to room temperature
20. additionthe mixture was treated with concentrated HCl
21. extractionextracted with ethyl acetate
22. extractionThe organic extract
23. washwas washed with water and brine
24. dry with materialdried (sodium sulfate)
25. concentrationconcentrated

ORD record

ord-54bf20e7a9344035aa6469a3e7cf9776

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07109229B2