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

HRID 913967

반응식

HRID 913967 반응식
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]

참가 물질

6

반응물 3

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

생성물 1

HCID 575459895-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-7-vinyl-1H-indole-3-carbonitrile수율 72.7%

시약·촉매·용매 2

HCID 962Water용매HCID 3776Isopropanol용매

반응 조건

온도
90 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-e26708d7281842b187e67d94038d63e5
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026257B2

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