Iodine → 4-Iodo-6-methoxynicotinaldehyde

Temperatur

-78 °C

At −78° C., 25.1 ml (40.1 mmol, 1.1 eq.) of n-butyllithium were added to a solution of 5.7 ml (43.8 mmol, 1.2 eq.) of N,N,N′-trimethylethylenediamine in 135 ml of THF, the mixture was stirred for 45 min and 5.0 g (36.5 mmol) of 6-methoxypyridine-3-carbaldehyde were added. After 45 min at −78° C., a further 45.6 ml (72.9 mmol, 2.0 eq.) of n-butyllithium were added, the reaction mixture was stirred for 1 h, allowing the temperature to rise to −40° C., the mixture was stirred at −40° C. for a further 1 h and then cooled back to −78° C., and a solution of 18.5 g (72.9 mmol) of iodine in 90 ml of THF was added over a period of 50 min. The temperature was maintained at −78° C. for a further 4 h and then slowly allowed to rise to RT overnight. The reaction mixture was poured into 300 ml of saturated aqueous sodium chloride solution and, after phase separation, the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried (sodium sulphate), filtered and concentrated under reduced pressure. The residue was stirred with acetonitrile and filtered off, and the precipitate was dried under HV. Yield: 647 mg (purity 91%, 6% of theory)

1. waitAfter 45 min at −78° C.
2. stirringthe reaction mixture was stirred for 1 h
3. customto rise to −40° C.
4. stirringthe mixture was stirred at −40° C. for a further 1 h
5. temperatureThe temperature was maintained at −78° C. for a further 4 h
6. waitto rise to RT overnight
7. customafter phase separation
8. extractionthe aqueous phase was extracted twice with ethyl acetate
9. dry with materialThe combined organic phases were dried (sodium sulphate)
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. stirringThe residue was stirred with acetonitrile
13. filtrationfiltered off
14. customthe precipitate was dried under HV

ORD-Eintrag

ord-36c561bdf8df4e7db48a0ad9d78647ac

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09434690B2