Ethyl chloroformate → Ethyl 3,5-dibromoisonicotinate

Temperature

-78 °C

To a −78° C. solution of LDA (64 mL, 128 mmol, 2 M solution) in anhydrous THF (100 mL) was added a solution of 3,5-dibromopyridine (28 g, 118 mmol) in anhydrous THF (100 mL). The reaction mixture was stirred at −78° C. for 45 minutes. Then, a solution of ethyl chloroformate (100 mL, 105 mmol) was added slowly over 15 minutes. After stirring for 15 minutes, the reaction mixture was quenched with a saturated solution of NaHCO3 (250 mL). The mixture was extracted into ethyl acetate (3×150 mL). The combined organic extracts were extracted with brine (2×400 mL), dried over MgSO4, filtered, evaporated, and dried in vacuo. The crude product was purified by flash chromatography (0-20% ethyl acetate/hexane), affording ethyl 3,5-dibromopyridine-4-carboxylate (33 g, 91% yield).

1. stirringAfter stirring for 15 minutes
2. customthe reaction mixture was quenched with a saturated solution of NaHCO3 (250 mL)
3. extractionThe mixture was extracted into ethyl acetate (3×150 mL)
4. extractionThe combined organic extracts were extracted with brine (2×400 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. customevaporated
8. customdried in vacuo
9. customThe crude product was purified by flash chromatography (0-20% ethyl acetate/hexane)

ORD record

ord-db2da350c62942c5a85b899b45835418

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315521B2