Reaktion #41976

Reaktionsgleichung

benzyl chloroformate

7-aminoindole

CH2Cl2

NaOH

→

title compound

Ausbeute 96.7%

(1H-Indol-7-yl)-carbamic acid benzyl ester

Ausbeute 96.7%

Lösungsmittel

heptane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeEquip
2. 2
   workup.ADDITIONapparatus, addition funnel
3. 3
   SonstigeThoroughly purge the flask with nitrogen
4. 4
   TemperaturAfter cooling the biphasic solution to less than 10° C.
5. 5
   Temperaturto maintain the temperature at less than 10° C. over one hour
6. 6
   workup.STIRRINGStir
7. 7
   Sonstigethe reaction vigorously for 1 hour until complete by TLC
8. 8
   SonstigeSeparate the layers
9. 9
   Extraktionextract the aqueous layer with CH2Cl2 (1.7 L)
10. 10
    WaschenCombine the organic layers, wash with 2N NaOH (2×2 L)
11. 11
    Trocknendry over Na2SO4
12. 12
    FiltrationAfter filtering off the drying agent
13. 13
    Einengenconcentrate the filtrate in vacuo to a volume of ˜1.5 L
14. 14
    Sonstigeresulting in thin dark mixture
15. 15
    Sonstigeto form a thick sand-like slurry
16. 16
    EinengenConcentrate to a volume of ˜1.5 L
17. 17
    Filtrationfilter while hot (50-60° C.)
18. 18
    Waschenwash
19. 19
    Temperaturwith warm (45° C.) heptane (1 L) and RT heptane (1 L)
20. 20
    Sonstigedry

Vorschrift

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).

Quelle