Triethylamine → 5-Bromo-6-chloropyridine-2-carbonitrile

Temperatur

50 °C

Trimethylsilyl cyanide (19 mL, 0.15 mol) was added to a stirred solution of 3-bromo-2-chloropyridine 1-oxide (C27) (31.6 g, 0.152 mol) and triethylamine (63.4 mL, 0.46 mol) in acetonitrile (400 mL). The reaction mixture was heated to 50° C. for 2 hours. It was then cooled to room temperature and additional trimethylsilyl cyanide (19 mL, 0.15 mol) was added. After the reaction mixture was heated at 50° C. for 1.5 hours, a final portion of trimethylsilyl cyanide (28.5 mL, 0.23 mol) was added and the reaction was heated at reflux for 3 days. After dilution with dichloromethane (2 L), the reaction was washed with saturated aqueous sodium bicarbonate solution (800 mL), then with water (1 L), dried over magnesium sulfate and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 20% to 25% ethyl acetate in heptane) afforded the title compound as a yellow solid. Yield: 14.92 g, 68.6 mmol, 45%.

1. temperatureIt was then cooled to room temperature
2. temperatureAfter the reaction mixture was heated at 50° C. for 1.5 hours
3. temperaturethe reaction was heated
4. temperatureat reflux for 3 days
5. washAfter dilution with dichloromethane (2 L), the reaction was washed with saturated aqueous sodium bicarbonate solution (800 mL)
6. dry with materialwith water (1 L), dried over magnesium sulfate
7. concentrationconcentrated in vacuo
8. customPurification via silica gel chromatography (Gradient: 20% to 25% ethyl acetate in heptane)

ORD-Eintrag

ord-dd1498a90330439a9b0f87fa20d31b48

Quelldatensatz

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09067934B2