Ethyl 3-bromo-5-fluoropyridine-4-carboxylate → HCID 59589366, compound

Temperature

70 °C

To a solution of ethyl 3-bromo-5-fluoropyridine-4-carboxylate (4.8 g, 20 mmol) in anhydrous 1,4-dioxane (30 mL) at room temperature was added (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium (II) (325 mg, 0.43 mmol), followed by a diethylzinc solution (22 mL, 20 mmol, 1.1 M solution in toluene). The mixture was stirred at 70° C. for 45 minutes. After cooling to room temperature, the reaction was quenched with MeOH. Ethyl acetate (100 mL) was added. The mixture was extracted with 0.1 N HCl (200 mL). The organic layer was recovered. The pH of the aqueous phase was brought to 6 with 2 N NaOH. The mixture was extracted with EtOAc (1×100 mL). The combined organic extracts were dried over MgSO4, filtered, evaporated, and dried in vacuo. The crude product was purified by flash chromatography (0-20% ethyl acetate/hexane), affording ethyl 3-ethyl-5-fluoropyridine-4-carboxylate (2.0 g, 51% yield)

1. temperatureAfter cooling to room temperature
2. customthe reaction was quenched with MeOH
3. additionEthyl acetate (100 mL) was added
4. extractionThe mixture was extracted with 0.1 N HCl (200 mL)
5. customThe organic layer was recovered
6. extractionThe mixture was extracted with EtOAc (1×100 mL)
7. dry with materialThe combined organic extracts were dried over MgSO4
8. filtrationfiltered
9. customevaporated
10. customdried in vacuo
11. customThe crude product was purified by flash chromatography (0-20% ethyl acetate/hexane)

ORD record

ord-029cc491a0f541bdb1b47204480900e7

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315521B2