Diethyl Malonate → 3-Acetyl-2-chloropyridine

Triethylamine (7.4 g, 73 mmol) was added to a solution of diethyl malonate (5.6 g, 35 mmol) and anhydrous magnesium chloride (1.9 g, 20 mmol) in toluene (15 ml) under inert atmosphere. After stirring for 1 hr at room temperature, a solution of 2-chloro nicotinoyl chloride (5.2 g, 29 mmol) in toluene (5 ml) was added and the reaction mixture was stirred at room temperature for a further 1 hr. The reaction was quenched with ice cold 2N hydrochloric acid (20 ml), and the organic layer was separated and concentrated to dryness. The resultant residue was dissolved in a mixture of 3:2 DMSO-water and heated at 120-130° C. for 6 hr. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (100 ml). The organic layer was washed once with bicarbonate solution, then several times with water, and finally with brine. The organic layer was then dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure to yield 1-(2-chloro-pyridin-3-yl)ethanone (1 g, 25%) as oil.

1. stirringthe reaction mixture was stirred at room temperature for a further 1 hr
2. customThe reaction was quenched with ice cold 2N hydrochloric acid (20 ml)
3. customthe organic layer was separated
4. concentrationconcentrated to dryness
5. dissolutionThe resultant residue was dissolved in a mixture of 3:2 DMSO-water
6. temperatureheated at 120-130° C. for 6 hr
7. temperatureThe reaction mixture was cooled to room temperature
8. additiondiluted with ethyl acetate (100 ml)
9. washThe organic layer was washed once with bicarbonate solution
10. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated to dryness under reduced pressure

ORD record

ord-d73c6b33d0934d6c925fb6040e25f992

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486962B2