Water → 1-(4-Chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)ethanone

HRID 1506238Notes

Reaction equation

HRID 1506238 reaction equation
C[Mg]Br.[CH2:4](OCC)C.[Cl:9][C:10]1[C:15]([CH:16]=[O:17])=[CH:14][N:13]=[C:12]2[N:18]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:19]=[CH:20][C:11]=12.O.[Cl-].[NH4+]>O1CCCC1.[O-2].[O-2].[Mn+4]>[Cl:9][C:10]1[C:15]([C:16](=[O:17])[CH3:4])=[CH:14][N:13]=[C:12]2[N:18]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:19]=[CH:20][C:11]=12

Participants

7

Reactant 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 866767394-Chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrrolo[2,3-b]pyridine-5-carbaldehydeHCID 178467822HCID 178467822, compound

Product 1

HCID 712582001-(4-Chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)ethanoneYield 61%

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent

Procedure

Methylmagnesium bromide-diethyl ether solution (3.0 M, 10 mL, 30 mmol) was added dropwise to 4-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde (4.89 g, 15.7 mmol) obtained in Reference Synthetic Exampleb 55 in tetrahydrofuran (50 mL) under cooling with ice, and the reaction mixture was stirred for 2 hours. After dropwise addition of water and addition of saturated aqueous ammonium chloride, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in 1,2-dimethoxyethane (25 mL) and vigorously stirred with manganese dioxide (9.0 g, 0.10 mol) at 80° C. for 4 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in 1,2-dimethoxyethane (25 mL) and vigorously stirred with manganese dioxide (9.0 g, 0.10 mol) at 80° C. for 4 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1 (v/v)) to give the title compound as an orange oil (3.09 g, yield 61%). (alternative to Reference Synthetic Exampleb 33)

Workup

  1. temperatureunder cooling with ice
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in 1,2-dimethoxyethane (25 mL)
  6. filtrationThe reaction mixture was filtered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. dissolutionThe residue was dissolved in 1,2-dimethoxyethane (25 mL)
  9. filtrationThe reaction mixture was filtered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1 (v/v))

Sources & evidence

ORD record
ord-588ab01f137749a8a885e7b3ac58801b
Source dataset
uspto-grants-2015_12
Patent number
US09216999B2

Reaction notes

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