Sodium hydride → 4-Chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrrolo[3,2-c]pyridine

Temperatur

0 °C

A mixture of 4-chloro-1H-pyrrolo[3,2-c]pyridine (98%, 2.0 g, 13 mmol) and tetrahydrofuran (20 mL) was cooled to 0° C. Sodium hydride (60% in oil, 1.03 g, 25.8 mmol) was added portion-wise over 5 minutes, and the reaction mixture was allowed to stir at 0° C. for 10 minutes. 2-(Trimethylsilyl)ethoxymethyl chloride (3.40 mL, 19.3 mmol) was then added drop-wise over 5 minutes, and stirring was continued at 0° C. for 15 minutes. The reaction mixture was quenched with saturated aqueous ammonium chloride solution; the aqueous layer was extracted twice with ethyl acetate, and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 10% to 20% ethyl acetate in heptane) afforded the product as a colorless oil. Yield: 2.64 g, 9.33 mmol, 72%. LCMS m/z 283.0 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J=5.8 Hz, 1H), 7.34 (dd, J=5.8, 0.7 Hz, 1H), 7.25 (d, J=3.3 Hz, 1H), 6.69 (dd, J=3.3, 0.7 Hz, 1H), 5.48 (s, 2H), 3.46 (dd, J=8.2, 8.1 Hz, 2H), 0.89 (dd, J=8.2, 8.1 Hz, 2H), −0.05 (s, 9H).

1. stirringstirring
2. waitwas continued at 0° C. for 15 minutes
3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution
4. extractionthe aqueous layer was extracted twice with ethyl acetate
5. dry with materialthe combined organic layers were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD-Eintrag

ord-53788ef2e0e34a239bd3eebf309d2748

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08822494B2