1,2-Dichloroethane → Ethyl 2,6-dichloro-5-fluoro-beta-oxo-3-pyridinepropionate

Temperature

90 °C

To 100 □ of 1,2-dichloroethane were added 10 g of 2,6-dichloro-5-fluoro-3-cyanopyridine, 3.6 g of zinc chloride, and 11 g of potassium ethylmalonate, and then the mixture was stirred at reflux. After the reaction was completed, 50 □ of 6 N hydrochloric acid was added to the mixture, which then was stirred at reflux at 90° C. for 4 hours. After confirming completion of the reaction by TLC, the solution was cooled to 20° C., and then an organic layer was separated therefrom. The organic layer was dried through distillation under reduced pressure, and 50 □ of a mixed solvent of ethanol and water ( 7:3, v/v ) was added thereto. Then, the reactor was cooled to 0˜10° C., and was stirred for 1 hour. The resulting solid was filtered and washed with 25 □ of a mixed solvent of ethanol and water ( 7:3, v/v ) having the same temperature, to obtain the title compound in the yield of 80% (11.7 g)

1. temperatureat reflux
2. stirringthen was stirred
3. customcompletion of the reaction by TLC
4. temperaturethe solution was cooled to 20° C.
5. customan organic layer was separated
6. dry with materialThe organic layer was dried through distillation under reduced pressure, and 50 □ of a mixed solvent of ethanol and water ( 7:3
7. additionv/v ) was added
8. temperatureThen, the reactor was cooled to 0˜10° C.
9. stirringwas stirred for 1 hour
10. filtrationThe resulting solid was filtered
11. washwashed with 25 □ of a mixed solvent of ethanol and water ( 7:3

ORD record

ord-361970655e7f41bca6144f2773133d95

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07642356B2