Hexachloroethane → 5-Chloro-6-methoxypicolinaldehyde

Temperature

-78 °C

A solution of methylpiperazine (2.31 g) in tetrahydrofuran (20 mL) was cooled to −78° C., and n-butyllithium (2.64 M, 7.55 mL) was added dropwise in an argon gas atmosphere. After stirring at the same temperature for 15 minutes, a solution of 6-methoxypicolinaldehyde (2.5 g) in tetrahydrofuran was added and the mixture was stirred for 30 minutes. t-Butyllithium (1.59 M, 17.1 mL) was added dropwise to the reaction solution, and the mixture was stirred at the same temperature for one hour and at −40° C. for 15 minutes. The reaction solution was cooled again to −78° C. A solution of hexachloroethane (12.9 g) in tetrahydrofuran (20 mL) was slowly added dropwise, and the mixture was stirred at the same temperature for 30 minutes. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered, after which the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1→10:1) to give 5-chloro-6-methoxypyridine-2-carbaldehyde as a colorless powder (1.21 g).

1. stirringthe mixture was stirred for 30 minutes
2. stirringthe mixture was stirred at the same temperature for one hour and at −40° C. for 15 minutes
3. stirringthe mixture was stirred at the same temperature for 30 minutes
4. extractionfollowed by extraction with ethyl acetate
5. washThe organic layer was washed with brine
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationafter which the filtrate was concentrated under reduced pressure
9. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1→10:1)

ORD record

ord-8f8113c61756436d835c99b67bba97c2

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822503B2