Triethylamine → 5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-7-vinyl-1H-indole-3-carbonitrile

HRID 913967

Reaktionsgleichung

Reaktionsgleichung von HRID 913967
Br[C:2]1[CH:3]=[C:4]([Cl:21])[CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:8]=[C:7]2[C:19]#[N:20].[CH:22]([B-](F)(F)F)=[CH2:23].[K+].C(N(CC)CC)C>CC(O)C.O>[Cl:21][C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([CH:22]=[CH2:23])[CH:3]=1)[N:9]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:8]=[C:7]2[C:19]#[N:20]

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 23679353Potassium vinyltrifluoroborateHCID 575460027-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile

Produkt 1

HCID 575459895-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-7-vinyl-1H-indole-3-carbonitrileAusbeute 72,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A solution of 7-bromo-5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indole-3-carbonitrile (620 mg, 1.607 mmol), Potassium vinyltrifluoroborate (237 mg, 1.768 mmol), and triethylamine (0.672 mL, 4.82 mmol) in 2-Propanol (50 mL) and Water (25 mL) was degassed with nitrogen for 10 min, then 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (66.1 mg, 0.080 mmol) was added and the reaction was sealed and heated at 90° C. for 2.5 hours. TLC indicated starting material was consumed and one major product plus byproducts were produced. The reaction was evaporated to remove most of the solvent, then the reaction was taken up in brine (10 mL) and extracted with ethyl acetate (3×10 mL). The organic layer was dried with MgSO4 and evaporated. The residue was purified by chromatography on SiO2 with 10% ethyl acetate/hexanes to give product 5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-7-vinyl-1H-indole-3-carbonitrile (389 mg, 1.169 mmol, 72.7% yield) as a yellow oil which crystallized to a yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 7.65 (d, J=2.0 Hz, 1H), 7.60 (s, 1H), 7.42 (dd, J=17.1, 10.8 Hz, 1H), 7.33 (d, 2.0 Hz, 1H), 5.71 (dd, J=17.2, 1.3 Hz, 1H), 5.48 (s, 2H), 5.47 (dd, J=10.8, 1.3 Hz, 1H), 3.51 (app t, J=8.0 Hz, 2H), 0.90 (app t, J=8.0 Hz, 2H), −0.05 (s, 9H). LC/MS (HPLC method 4): tR=4.30 min, 333.13(MH)+.

Aufarbeitung

  1. addition1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (66.1 mg, 0.080 mmol) was added
  2. customthe reaction was sealed
  3. customwas consumed
  4. customone major product plus byproducts were produced
  5. customThe reaction was evaporated
  6. customto remove most of the solvent
  7. extractionextracted with ethyl acetate (3×10 mL)
  8. dry with materialThe organic layer was dried with MgSO4
  9. customevaporated
  10. customThe residue was purified by chromatography on SiO2 with 10% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-e26708d7281842b187e67d94038d63e5
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026257B2

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