Methyl chloroformate → Methyl 4-bromo-2-chloronicotinate

Temperature

-80 °C

A solution of 4-bromo-2-chloro-pyridine (4.5 mL, 41 mmol) in anhydrous THF (60 mL) was added dropwise to a stirred solution of lithium diisopropylamide (1.8 M in THF, 25 mL, 45 mmol) in anhydrous THF (60 mL) at −85° C. After stirring for 30 min at −80° C., the reaction mixture was added dropwise via cannula to a stirred solution of methylchloroformate (31 mL, 400 mmol) in anhydrous THF at −80° C. After stirring for 50 min at −80° C., the reaction was quenched by the addition of concentrated aqueous NaHCO3 (90 mL), and subsequently diluted with EA (250 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with hexane/EA 4:1) to give the title compound. MS (m/z): 252.0.1 [M+H+].

1. stirringAfter stirring for 50 min at −80° C.
2. customthe reaction was quenched by the addition of concentrated aqueous NaHCO3 (90 mL)
3. additionsubsequently diluted with EA (250 mL)
4. dry with materialThe organic layer was dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash chromatography on silica gel (elution with hexane/EA 4:1)

ORD record

ord-e27ab119413f423d9948b6345d61ca40

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410134B2