Methyl chloroformate → Methyl 4-iodo-2-methoxynicotinate

Temperature

-10 °C

To a solution of diisopropylamine (10.4 mL) in THF (150 mL) was added 1.6M n-butyllithium hexane solution (46 mL) under argon atmosphere at −10° C., and the mixture was stirred under argon atmosphere at −10° C. for 30 min. To the reaction mixture was slowly added a solution of 2-fluoro-3-iodopyridine (15 g) in THF (100 mL) at −78° C., and the mixture was stirred under argon atmosphere at −78° C. to −60° C. for 3 hr. To the reaction mixture was slowly added methyl chloroformate (7.21 g) at −78° C., and the mixture was stirred under argon atmosphere at −78° C. for 30 min. To the reaction mixture was slowly added a solution of sodium methoxide (3.90 g) in methanol (45 mL) at −78° C., and the mixture was allowed to be warmed to room temperature, and stirred at room temperature for 1 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (10 g).

1. stirringthe mixture was stirred under argon atmosphere at −78° C. to −60° C. for 3 hr
2. customat −78° C.
3. stirringthe mixture was stirred under argon atmosphere at −78° C. for 30 min
4. temperatureto be warmed to room temperature
5. stirringstirred at room temperature for 1 hr
6. extractionthe mixture was extracted with ethyl acetate
7. washThe organic layer was washed with saturated brine
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

ORD record

ord-21d12706709a4d1c869b01a8cfe28868

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09371320B2