Diethyl Malonate → 5-(5-Chloro-2-fluorophenyl)cyclohexane-1,3-dione

To a solution of 20% sodium ethoxide in ethanol (7.4 g) was added at room temperature diethyl malonate (3.6 g), and then added little by little 4-(5-chloro-2-fluorophenyl)-3-buten-2-one (4.3 g). The mixture was stirred at room temperature for 30 minutes and then for 2 hours while heating, and cooled. The solvent was evaporated, and to the residue was added water. The aqueous layer was washed with ethyl acetate and concentrated. To the residue was added 2M sodium hydroxide (17 ml), and the mixture was refluxed for 1 hour and cooled. To the mixture was added 2.5M sulfuric acid (17 ml) for 10 minutes, and the mixture was refluxed for 30 minutes and cooled. Precipitated crystals were filtered and washed with water and isopropylether to give 5-(5-chloro-2-fluorophenyl)cyclohexane-1,3-dione (4.1 g) as pale yellow crystals.

1. temperaturefor 2 hours while heating
2. temperaturecooled
3. customThe solvent was evaporated
4. additionto the residue was added water
5. washThe aqueous layer was washed with ethyl acetate
6. concentrationconcentrated
7. additionTo the residue was added 2M sodium hydroxide (17 ml)
8. temperaturethe mixture was refluxed for 1 hour
9. temperaturecooled
10. additionTo the mixture was added 2.5M sulfuric acid (17 ml) for 10 minutes
11. temperaturethe mixture was refluxed for 30 minutes
12. temperaturecooled
13. customPrecipitated crystals
14. filtrationwere filtered
15. washwashed with water and isopropylether

ORD record

ord-822be905131044cda55051db61b2f40f

Source dataset

uspto-grants-2002_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06350749B1