Reaktion #1770480

Reaktionsgleichung

5-Bromo-1-triisopropylsilylindole

tert-Butyllithium

NaCl

tetra-n-butylammonium fluoride

benzaldehyde

phenyl(indol-5-yl)methanol

→

5-benzylindole

required product

1-(N,N-Dimethylamino)-2-(5-benzylindol-3-yl)ethane

Lösungsmittel

EtOH

THF

THF

H2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   workup.ADDITIONby the time addition
3. 3
   Sonstigea permanent yellow coloration had been produced
4. 4
   workup.ADDITIONwere added to the mixture which
5. 5
   Extraktionwas then extracted (3×) with Et2O
6. 6
   Waschenwashed (H2O, 3×
7. 7
   Trocknensaturated aqueous NaCl) and dried (MgSO4)
8. 8
   SonstigeEvaporation
9. 9
   Sonstigegave a gum which
10. 10
    Sonstigewas chromatographed (silica gel; hexane/Et2O; 0-30%)
11. 11
    SonstigeRecovered
12. 12
    Wascheneluted first
13. 13
    workup.ADDITIONseveral fractions containing contaminated product
14. 14
    Sonstigewere subsequently obtained)
15. 15
    workup.STIRRINGThe mixture was stirred for 1.5 hr
16. 16
    Sonstigepartitioned between Et2O and saturated aqueous NaCl
17. 17
    ExtraktionAfter re-extracting the aqueous layer (Et2O; 2×)
18. 18
    Waschenthe combined ethereal layers were washed with saturated aqueous NaCl
19. 19
    Trocknendried (MgSO4)
20. 20
    Sonstigeevaporated to a gum which
21. 21
    Sonstigewas chromatographed (silica gel; hexane/Et2O; 0-50%)
22. 22
    Sonstigegiving
23. 23
    workup.ADDITIONa total of 0.30 g was added over the reaction period, in two portions), at 45 psi
24. 24
    workup.WAITfor ca 40 hr
25. 25
    FiltrationThe catalyst was filtered off
26. 26
    Sonstigethe filtrate evaporated to a gum which
27. 27
    Sonstigewas chromatographed (silica gel; hexane/Et2O; 0-50%)

Vorschrift

5-Bromo-1-triisopropylsilylindole (2.0 g, 5.68 mmol) was dissolved in THF (dry, 30 mL) and the solution cooled to -70° C. tert-Butyllithium (1.7M in hexane; 10.7 mL, 18.2 mmol) was added, and by the time addition was complete, a permanent yellow coloration had been produced. After a further 1 hr at -65° C. benzaldehyde (0.658 g, 6.20 mmol) was added and the mixture stirred at ca -65° C. for 1 hr before warming gradually to room temperature H2O and NaCl were added to the mixture which was then extracted (3×) with Et2O, and the extracts were combined, washed (H2O, 3× and then saturated aqueous NaCl) and dried (MgSO4). Evaporation gave a gum which was chromatographed (silica gel; hexane/Et2O; 0-30%). Recovered starting material, 0.437 g (22%) eluted first; followed by the product: phenyl(1-triisopropylsilylindol-5-yl)methanol, a gum which solidified on standing, 0.61 g (28%; several fractions containing contaminated product were subsequently obtained). The pure product (0.6 g, 1.58 mmol) was dissolved in THF (10 mL) and treated with tetra-n-butylammonium fluoride solution (1.0M in THF; 3.0 mL) at room temperature. The mixture was stirred for 1.5 hr and then partitioned between Et2O and saturated aqueous NaCl. After re-extracting the aqueous layer (Et2O; 2×), the combined ethereal layers were washed with saturated aqueous NaCl, dried (MgSO4) and evaporated to a gum which was chromatographed (silica gel; hexane/Et2O; 0-50%), giving: phenyl(indol-5-yl)methanol, as an almost colourless gum, 0.347 g (98%). This material was hydrogenated in EtOH (25 mL) over Pd-C (5%; a total of 0.30 g was added over the reaction period, in two portions), at 45 psi, for ca 40 hr. The catalyst was filtered off, and the filtrate evaporated to a gum which was chromatographed (silica gel; hexane/Et2O; 0-50%). The required product: 5-benzylindole, was obtained as an off white solid, 0.135 g (44%), as well as 5-benzylindoline 0.03 g, (10%) and unreacted starting material, 0.013 g (4%).

Quelle