반응 #41976

반응 방정식

benzyl chloroformate

7-aminoindole

CH2Cl2

NaOH

→

title compound

수율 96.7%

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

수율 96.7%

용매

heptane

반응 조건

후처리

1. 1
   기타Equip
2. 2
   workup.ADDITIONapparatus, addition funnel
3. 3
   기타Thoroughly purge the flask with nitrogen
4. 4
   온도After cooling the biphasic solution to less than 10° C.
5. 5
   온도to maintain the temperature at less than 10° C. over one hour
6. 6
   workup.STIRRINGStir
7. 7
   기타the reaction vigorously for 1 hour until complete by TLC
8. 8
   기타Separate the layers
9. 9
   추출extract the aqueous layer with CH2Cl2 (1.7 L)
10. 10
    세척Combine the organic layers, wash with 2N NaOH (2×2 L)
11. 11
    건조dry over Na2SO4
12. 12
    여과After filtering off the drying agent
13. 13
    농축concentrate the filtrate in vacuo to a volume of ˜1.5 L
14. 14
    기타resulting in thin dark mixture
15. 15
    기타to form a thick sand-like slurry
16. 16
    농축Concentrate to a volume of ˜1.5 L
17. 17
    여과filter while hot (50-60° C.)
18. 18
    세척wash
19. 19
    온도with warm (45° C.) heptane (1 L) and RT heptane (1 L)
20. 20
    기타dry

실험 절차

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).

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