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

Temperature

70 °C

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 reaction mixture was cooled to room temperature and then was quenched with MeOH. The resulting mixture was extracted with ethyl acetate (2×100 mL), and the organic layer was washed with water, 0.1 N HCl, and brine. The organic layer was then dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated, and the residue was purified by CombiFlash using 0-30% ethyl acetate and 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.

1. temperatureThe reaction mixture was cooled to room temperature
2. customwas quenched with MeOH
3. extractionThe resulting mixture was extracted with ethyl acetate (2×100 mL)
4. washthe organic layer was washed with water, 0.1 N HCl, and brine
5. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
6. filtrationfiltered
7. customThe filtrate was evaporated
8. customthe residue was purified by CombiFlash

ORD record

ord-66ef3da0fb8c437dbbd5a84d03a28442

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315521B2