Ethyl 3-bromo-5-chloropyridine-4-carboxylate → Ethyl 5-chloro-3-ethylpyridine-4-carboxylate

HRID 577101Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:13])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH2:14]([Zn]CC)[CH3:15]>O1CCOCC1>[Cl:13][C:6]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:2]([CH2:14][CH3:15])[CH:3]=[N:4][CH:5]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of ethyl 3-bromo-5-chloropyridine-4-carboxylate (5.84 g, 22.08 mmol) in anhydrous dioxane (40 mL) at room temperature was added (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium (II) (323 mg, 0.441 mmol). Then, diethylzinc (2.72 g, 18 mL, 22.09 mmol, 15% solution in toluene) was added dropwise and the reaction was heated at 70° C. for 45 minutes. The mixture was cooled to room temperature, quenched with MeOH, and extracted with ethyl acetate (2×100 mL). The organic layer was washed with water, 0.1 N HCl, and brine, and then dried over anhydrous sodium sulfate. The filtered solution was evaporated, and the residue was purified by CombiFlash using 0-30% ethyl acetate in hexane to provide ethyl 5-chloro-3-ethylpyridine-4-carboxylate as a pale yellow oil (2.59 g, 55% yield); 1H NMR (400 MHz, CDCl3): δ 1.25 (t, 3H), 1.45 (t, 3H), 2.65 (q, 2H), 4.47 (q, 2H), 8.41 (s, 1H), 8.49 (s, 1H); M+ 214.5.

Workup

temperatureThe mixture was cooled to room temperature
customquenched with MeOH
extractionextracted with ethyl acetate (2×100 mL)
washThe organic layer was washed with water, 0.1 N HCl, and brine
dry with materialdried over anhydrous sodium sulfate
customThe filtered solution was evaporated
customthe residue was purified by CombiFlash

Sources & evidence

ORD record: ord-e66fde6ec6244bba9d413e318f280ea5
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040538B2

Reaction notes

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