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 and cooled to −78° C. was added a solution of 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 mixture was extracted into ethyl acetate (3×100 mL), and the combined organic layers were washed with water and brine. The separated organic layer was 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 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 mixture was extracted into ethyl acetate (3×100 mL)
4. washthe combined organic layers were washed with water and brine
5. dry with materialThe separated organic layer was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. customThe filtrate was evaporated
8. customthe residue was purified through CombiFlash

ORDレコード

ord-9ddb7068d202459e8c10cb835ed50ee5

出典データセット

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09315521B2