Dimethylcarbamoyl Chloride → 4-Methoxypyridine-2-carbonitrile

To a slurry of 4-methoxypyridine N-oxide hydrate, 50 g, in 250 mL of chloroform was added 20 g of magnesium sulfate. The slurry was stirred for 1 hour at ambient temperature, then filtered and concentrated to dryness. To a solution of the residue, 4-methoxypyridine N-oxide, 43 g (350 mmol) in 350 mL of dichloromethane was added 65 mL (490 mmol) of trimethylsilylcyanide. The solution was cooled to 10° C. and 45 mL (490 mmol) of N,N-dimethylcarbamyl chloride was added dropwise such that the reaction warmed to a gentle reflux. Upon completion of the addition, the reaction mixture was stirred overnight at ambient temperature, then carefully quenched at 0° C. dropwise with 10% aqueous potassium carbonate. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. The residue was triturated with ether. Filtration of the solid provided 31.4 g (67%) of the desired product as a white solid. 1H—NMR is consistent with structure; MS (ion spray) 135.1 (M+).

1. filtrationfiltered
2. concentrationconcentrated to dryness
3. temperatureThe solution was cooled to 10° C.
4. temperaturewarmed to a gentle reflux
5. additionUpon completion of the addition
6. stirringthe reaction mixture was stirred overnight at ambient temperature
7. customcarefully quenched at 0° C. dropwise with 10% aqueous potassium carbonate
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with dichloromethane
10. washThe combined organics were washed with brine
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated to dryness
14. customThe residue was triturated with ether
15. filtrationFiltration of the solid

ORD-Eintrag

ord-93bfeefd9db44b969b485863bf2f871f

Quelldatensatz

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06743794B2