Hydrochloric Acid → Ethyl 3-(2-fluoro-4-pyridyl)-3-oxopropionate

To a solution of 2-fluoro-4-pyridinecarboxylic acid (10 g, 70.9 mmol) in tetrahydrofuran (150 ml) was added 1,1′-carbonylbis-1H-imidazole (12.7 g, 78.0 mmol), and the mixture was heated under reflux for 30 min. The reaction solution was cooled and monoethyl malonate magnesium salt (11.2 g, 39.0 mmol) was added. The mixture was stirred at room temperature for 30 min. 1N Hydrochloric acid (200 ml) was added to the reaction solution, and the mixture was extracted with ethyl acetate (200 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) and recrystallized from hexane to give ethyl 3-(2-fluoro-4-pyridyl)-3-oxopropionate (7.32 g, 49%).

1. temperaturethe mixture was heated
2. temperatureunder reflux for 30 min
3. temperatureThe reaction solution was cooled
4. extractionthe mixture was extracted with ethyl acetate (200 ml×2)
5. washThe extract was washed with saturated brine
6. dry with materialdried over anhydrous magnesium sulfate
7. customevaporated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)
9. customrecrystallized from hexane

ORD record

ord-ab864b988d2c4f138a755e23253dba79

Source dataset

uspto-grants-2006_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06982348B2