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

Temperature

-60 °C

5-Chloropyridine-2-carbonitrile (10.71 g, 77 mmol) was dissolved in diethylether (65 mL) and THF (35 mL) under a nitrogen atmosphere. The mixture was cooled until the internal temperature was −63° C. Methyl magnesium 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. 50 mL of THF was added to dissolve any precipitated material. After 1 h at room temperature the reaction was judged complete by HPLC. 2M hydrochloric acid (aq., 100 mL) was added and the reaction mixture was stirred for 4 h. pH was adjusted to 7 with sodium bicarbonate. The phases were separated and the product extracted from the aqueous phase twice with DCM. The combined organic extracts were dried over sodium sulphate and concentrated in vacuo. The product was purified by column chromatography (eluent heptane: ethyl acetate 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. waitAfter 1 h at room temperature the reaction was judged complete by HPLC
7. stirringthe reaction mixture was stirred for 4 h.
8. customThe phases were separated
9. extractionthe product extracted from the aqueous phase twice with DCM
10. dry with materialThe combined organic extracts were dried over sodium sulphate
11. concentrationconcentrated in vacuo
12. customThe product was purified by column chromatography (eluent heptane: ethyl acetate gradient)

ORD record

ord-97bc12de42db4f4c82fb23a15718d8dc

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07960395B2