1-Methylimidazole → (1-Methyl-1H-imidazol-5-yl)(pyridin-3-yl)methanone

Temperatur

-78 °C

To a heat-gun dried flask containing 1-methyl-1H-imidazole (1.55 mL, 19.5 mmol) and THF (20 mL) at −78° C. was added 1.6 M n-BuLi in hexane (12.8 mL, 20.5 mmol). After stirring at −78° C. for 30 min, chlorotriethylsilane (3.3 mL, 19.7 mmol) in neat was introduced slowly. The mixture was stirred at −78° C. for 30 min. 1.6 M n-BuLi in hexane (12.8 mL, 20.5 mmol) was added, and the mixture was stirred for 45 min. A solution of N-methoxy-N-methylnicotinamide (2.70 g, 16.2 mmol, Intermediate 10, step a) in THF (20 mL) was added via cannula, and the mixture was stirred at −78° C. to room temperature for 2 hours. The reaction was quenched with NH4Cl (aqueous), the organic layer was separated, and the aqueous layer was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4), filtered, concentrated, and purified by flash column chromatography (40 g silica gel column, 50-100% EtOAc in heptane, then 5-10% MeOH in CH2Cl2) to obtain the title compound as an off-white solid.

1. customTo a heat-gun dried flask
2. stirringThe mixture was stirred at −78° C. for 30 min
3. stirringthe mixture was stirred for 45 min
4. stirringthe mixture was stirred at −78° C. to room temperature for 2 hours
5. customThe reaction was quenched with NH4Cl (aqueous)
6. customthe organic layer was separated
7. extractionthe aqueous layer was extracted with CH2Cl2
8. dry with materialThe combined organic phases were dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. custompurified by flash column chromatography (40 g silica gel column, 50-100% EtOAc in heptane

ORD-Eintrag

ord-eeb3e72309854c1481afc181307a9eb0

Quelldatensatz

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09309222B2