反应详情

2-Bromo-4-methyl-aniline (10.0 g, 53.7 mmol) was added dropwise to a solution of boron trichloride in methylene chloride (1.0 M, 60 mL, 60 mmol) cooled with ice water. The reaction mixture was warmed to room temperature, stirred for 30 min, and chloroacetonitrile (10 mL, 64.4 mmol) and aluminum chloride (10 g, 59.8 mmol) added, followed by 1,2-dichloroethane (70 mL). The reaction mixture was heated to 70° C. to distill off methylene chloride, and then refluxed for 24 hrs. The mixture was cooled to 0–5° C., treated with 25 M HCl (96 mL) at 0˜5° C. carefully, and then heated to 80° C. for 1 h until all solids dissolved. The aqueous layer was separated and extracted with methylene chloride. The combined organic layers were washed with water and brine, dried (sodium sulfate) and concentrated a yellow solid (11.6 g, 82.3%), that was used without-further purification. The crude product was taken into dioxane (76 mL) and water (8.5 mL), and treated with sodium borohydride (1.75 g, 46.3 mmol) in portions. After 30 min at room temperature, all the starting material was consumed, and the reaction mixture was heated to reflux for 14 h. The mixture was then cooled to room temperature, treated with 0.1 N HCl (74 mL), and extracted with ethyl acetate. The extract was washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography on silica gel (hexanes/ethyl acetate) gave 5-methyl-7-bromoindole (8.0 g, 90%). 1H NMR (400 MHz, CDCl3) 2.43 (s, 3H), 6.54 (dd, J1=1.94 Hz, J2=3.13 Hz, 1H), 7.20 (d, J=0.78 Hz, 1H), 7.22 (m, 1H), 7.36 (m, 1H), 8.22 (br, 1H); MS (ES, m/z): C9H8BrN: 210 (M+(79Br)+1), 212.0 (M+(81Br)+1).

1. temperatureThe reaction mixture was heated to 70° C.
2. distillationto distill off methylene chloride
3. temperaturerefluxed for 24 hrs
4. temperatureThe mixture was cooled to 0–5° C.
5. additiontreated with 25 M HCl (96 mL) at 0˜5° C. carefully
6. temperatureheated to 80° C. for 1 h until all solids
7. dissolutiondissolved
8. customThe aqueous layer was separated
9. extractionextracted with methylene chloride
10. washThe combined organic layers were washed with water and brine
11. dry with materialdried (sodium sulfate)
12. concentrationconcentrated a yellow solid (11.6 g, 82.3%), that
13. custompurification
14. waitAfter 30 min at room temperature
15. customall the starting material was consumed
16. temperaturethe reaction mixture was heated
17. temperatureto reflux for 14 h
18. temperatureThe mixture was then cooled to room temperature
19. additiontreated with 0.1 N HCl (74 mL)
20. extractionextracted with ethyl acetate
21. washThe extract was washed with water and brine
22. dry with materialdried (Na2SO4)
23. concentrationconcentrated