Pyridine → Methyl 3-(2-chloro-6-fluorophenyl)-3-oxopropanoate

To 7.4 g (77.7 mmol) of magnesium chloride and 9.02 g (116.1 mmol) of methyl acetoacetate was added 30 mL acetonitrile. The mixture was cooled in an ice bath and 12.6 mL (155.4 mmol) of pyridine was slowly added while keeping the temperature below 5° C. The reaction was removed from the ice bath and was stirred for 30 min. at room temperature. A solution of 15.0 g (77.7 mmol) 2-chloro-6-fluorobenzoyl chloride in 20 mL toluene was added to the reaction and the mixture was subsequently refluxed for four hours. The reaction was then cooled to room temperature and carefully treated with 6.5 mL (98.1 mmol) of concentrated sulfuric acid. The reaction was diluted with water and the layers were separated. The aqueous layer was extracted with dichloromethane and the combined organic layers were dried over sodium sulfate and concentrated to a residue. The residue was purified by flash chromatography eluting with 15% ethyl acetate/hexanes mixture to give 14.0 g (78%) of the title compound as a reddish-pink oil.

1. temperatureThe mixture was cooled in an ice bath
2. customthe temperature below 5° C
3. customThe reaction was removed from the ice bath
4. temperaturethe mixture was subsequently refluxed for four hours
5. temperatureThe reaction was then cooled to room temperature
6. customthe layers were separated
7. extractionThe aqueous layer was extracted with dichloromethane
8. dry with materialthe combined organic layers were dried over sodium sulfate
9. concentrationconcentrated to a residue
10. customThe residue was purified by flash chromatography
11. washeluting with 15% ethyl acetate/hexanes mixture

ORD record

ord-3a21ab407fcb4aaaa78f28c196481537

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07897607B2