Isonicotinic Acid → Ethyl 3-(4-pyridyl)-3-oxopropionate

Temperature

50 °C

Isonicotinic acid (35.56 g, 289 mmol) was added to a solution of 1,1′-carbonylbis-1H-imidazole (46.98 g, 290 mmol) in tetrahydrofuran (700 ml), and the resulting solution was stirred for 1.5 hr at 50° C. After cooling to room temperature, malonic acid monoester potassium salt (51.7 g, 304 mmol) and magnesium chloride (34.33 g, 361 mmol) were added, and the mixture was refluxed for 1 hr and then heated at 50° C. for 6 hr. The solvent was removed under reduced pressure and the residue was quenched by the addition of dilute acetic acid. The organic layer was extracted with ethyl acetate (3 times) and the combined extracts were washed with dilute aqueous sodium bicarbonate and brine, and were concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=2/1 to 1/1) and recrystallization from hexane-ethyl acetate gave 41.52 g (74%) of the title compound.

1. temperatureAfter cooling to room temperature
2. temperaturethe mixture was refluxed for 1 hr
3. temperatureheated at 50° C. for 6 hr
4. customThe solvent was removed under reduced pressure
5. customthe residue was quenched by the addition of dilute acetic acid
6. extractionThe organic layer was extracted with ethyl acetate (3 times)
7. washthe combined extracts were washed with dilute aqueous sodium bicarbonate and brine
8. concentrationwere concentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=2/1 to 1/1) and recrystallization from hexane-ethyl acetate

ORD record

ord-0ad56de7715a4fe89a5e64e4a6ea753f

Source dataset

uspto-grants-2005_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06844335B2