反应详情

温度

55 °C

Equip a 12-L reaction flask with a cooling bath, air driven stirring apparatus, addition funnel, and thermometer probe. Thoroughly purge the flask with nitrogen, charge 7-aminoindole (352 g, 2.663 moles), CH2Cl2 (5.30 L, 15 volumes) and 2N NaOH (1.76 L, 3.515 moles). After cooling the biphasic solution to less than 10° C., benzyl chloroformate (500 g, 2.929 moles) add dropwise at such a rate so as to maintain the temperature at less than 10° C. over one hour. Stir the reaction vigorously for 1 hour until complete by TLC. Separate the layers and extract the aqueous layer with CH2Cl2 (1.7 L). Combine the organic layers, wash with 2N NaOH (2×2 L), and dry over Na2SO4. After filtering off the drying agent, concentrate the filtrate in vacuo to a volume of ˜1.5 L resulting in thin dark mixture. Gradually exchange the solvent using heptane (˜4 L) to form a thick sand-like slurry and increase the bath temperature to 50-60° C. Concentrate to a volume of ˜1.5 L, filter while hot (50-60° C.), wash with warm (45° C.) heptane (1 L) and RT heptane (1 L), and dry to yield 683.5 g (96.7%) of the title compound as light purple solid. 1H-NMR(DMSO-d6, 300 MHz), δ 10.79 (br s, 1H), 9.42 (br s, 1H), 7.20-7.56 (m, 8H), 6.92 (t, 1H), 6.41 (dd, 1H), 5.18(s, 1H).

1. customEquip
2. additionapparatus, addition funnel
3. customThoroughly purge the flask with nitrogen
4. temperatureAfter cooling the biphasic solution to less than 10° C.
5. temperatureto maintain the temperature at less than 10° C. over one hour
6. stirringStir
7. customthe reaction vigorously for 1 hour until complete by TLC
8. customSeparate the layers
9. extractionextract the aqueous layer with CH2Cl2 (1.7 L)
10. washCombine the organic layers, wash with 2N NaOH (2×2 L)
11. dry with materialdry over Na2SO4
12. filtrationAfter filtering off the drying agent
13. concentrationconcentrate the filtrate in vacuo to a volume of ˜1.5 L
14. customresulting in thin dark mixture
15. customto form a thick sand-like slurry
16. concentrationConcentrate to a volume of ˜1.5 L
17. filtrationfilter while hot (50-60° C.)
18. washwash
19. temperaturewith warm (45° C.) heptane (1 L) and RT heptane (1 L)
20. customdry