反应详情

To a solution of aldehyde product from Step B (2.0 g, 14 mmol) in methanol (100 mL), 40% methylamine in water (2.27 mL, 27.6 mmol) was added at room temperature over a period of 10 min. The mixture was stirred at room temperature under nitrogen overnight and then was cooled down to 0° C. Sodium borohydride (1.05 g, 27.6 mmol) was added. The reaction mixture was slowly warmed to room temperature for 2 h. Most of methanol was removed in vacuo, and the residue was diluted with water and extracted (3×) with ether. The combined organic layers were extracted with 2 N HCl (100 mL). The HCl layer was made basic (pH ˜11) with 2 N NaOH and extracted (3×) with methylene chloride. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to give crude 4-(aminomethyl)-indole as a white powder (1.95 g, 88%): 1H NMR (300 MHz, CDCl3) δ8.29 (s, br, 1H), 7.31 (d, J=8.0 Hz, 1H), 7.22 (t, J=2.7 Hz, 1H), 7.16 (t, J=8.0, 7.3 Hz, 1H), 7.08 (d, J=7.3 Hz, 1H), 6.64 (t, J=2.0 Hz, 1H), 4.06 (s, 2H), 2.51 (s, 3H); CI MS m/z=160 [C10H12N2+H]+.

1. temperaturewas cooled down to 0° C
2. temperatureThe reaction mixture was slowly warmed to room temperature for 2 h
3. customMost of methanol was removed in vacuo
4. additionthe residue was diluted with water
5. extractionextracted (3×) with ether
6. extractionThe combined organic layers were extracted with 2 N HCl (100 mL)
7. extractionextracted (3×) with methylene chloride
8. washThe combined organic layers were washed with brine
9. dry with materialdried over Na2SO4
10. concentrationconcentrated in vacuo