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

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)

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))

ORD-Eintrag

ord-588ab01f137749a8a885e7b3ac58801b

Quelldatensatz

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09216999B2