Ethyl chloroformate → Ethyl 3-bromo-5-chloropyridine-4-carboxylate

To a solution of LDA (2 M solution in THF/heptane/ethylbenzene, 2.78 g, 12.97 mL, 25.95 mmol) in anhydrous THF (20 mL) under nitrogen atmosphere cooled to −78° C. was added a solution of the 3-bromo-5-chloropyridine (5.0 g, 25.98 mmol) in anhydrous THF (40 mL) at −78° C. The reaction mixture was allowed to stir at the same temperature for 45 minutes. Then, a solution of chloro(ethoxy)methanone (28.19 g, 259.7 mmol) was added slowly over 15 minutes. After stirring for 20 minutes, the reaction mixture was quenched with saturated NaHCO3 solution. The reaction mixture was extracted into ethyl acetate (3×100 mL), and the combined organic layer was washed with water and brine. The organic layer was separated, dried over anhydrous sodium sulfate, and filtered. The filtrate was evaporated, and the residue was purified through CombiFlash using 0-10% ethyl acetate in hexane to provide ethyl 3-bromo-5-chloropyridine-4-carboxylate as a pale yellow oil (5.84 g, 85% yield); 1H NMR (400 MHz, DMSO-d6): δ 1.35 (t, 3H), 4.45 (q, 2H), 8.82 (s, 1H), 8.87 (s, 1H); M+265.5.

1. stirringAfter stirring for 20 minutes
2. customthe reaction mixture was quenched with saturated NaHCO3 solution
3. extractionThe reaction mixture was extracted into ethyl acetate (3×100 mL)
4. washthe combined organic layer was washed with water and brine
5. customThe organic layer was separated
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. customThe filtrate was evaporated
9. customthe residue was purified through CombiFlash

ORDレコード

ord-2b0528ff56ba4e8f8df89bef4894f1a1

出典データセット

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09315521B2