Hydrochloric Acid → 1-(5-Chloropyridin-2-yl)ethan-1-one

Temperature

-60 °C

5-Chloropyridine-2-carbonitrile (10.7 g, 77 mmol) was dissolved in diethyl ether (65 mL) and THF (35 mL) under a nitrogen atmosphere. The mixture was cooled until the internal temperature was −63° C. Methylmagnesium bromide (3M in THF, 35 mL, 105 mmol) was added over 30 min. The reaction mixture was then left stirring at −60° C. for 45 min and was then warmed to room temperature. THF (50 mL) was added to dissolve any precipitated material and the reaction mixture was stirred for 1 h. 2M HCl aq. (100 mL) was added and the reaction mixture was stirred for 4 h. The pH was then adjusted to 7 with sodium bicarbonate. The phases were separated and the product extracted from the aqueous phase with DCM. The combined organic extracts were dried over sodium sulphate and concentrated in vacuo. The product was purified by flash column chromatography (eluent heptane:EtoAc gradient) to yield 7.9 g (64% yield) of the title compound.

1. temperatureThe mixture was cooled until the internal temperature
2. customwas −63° C
3. waitThe reaction mixture was then left
4. temperaturewas then warmed to room temperature
5. dissolutionto dissolve any precipitated material
6. stirringthe reaction mixture was stirred for 1 h
7. stirringthe reaction mixture was stirred for 4 h
8. customThe phases were separated
9. extractionthe product extracted from the aqueous phase with DCM
10. dry with materialThe combined organic extracts were dried over sodium sulphate
11. concentrationconcentrated in vacuo
12. customThe product was purified by flash column chromatography (eluent heptane:EtoAc gradient)

ORD record

ord-8214109d78f64f1ca219f28d27d1792f

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158785B2