Ethyl 3-bromo-5-fluoropyridine-4-carboxylate → HCID 59589366, compound
Reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:13])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH2:14]([Zn]CC)[CH3:15]>O1CCOCC1>[CH2:14]([C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:13])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:15]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 70 °C
Procedure
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)