4-Methylpyridine → HCID 67258297, Verbindung

Temperatur

-50 °C

To a solution of 4-methylpyridine (1 eq, 75 mmol) in anhydrous THF (50 mL) was added n-butyl lithium 2.5 M solution (1.3 eq, 98 mmol) at −50° C. under nitrogen. The reaction mixture was stirred for 30 min at −50° C. To the mixture was slowly added a solution of methyl 3-chloro-2-thiophenecarboxylate (1 eq, 75 mmol, synthesis described in Heterocycles, 2007, 71(1), 87) in anhydrous THF (50 mL) at −50° C. The reaction mixture was stirred at −50° C. for 30 min, then allowed to warm to room temperature and stirred for 2 h. The mixture was quenched with aqueous saturated ammonium chloride solution (150 mL). The organic layer was separated and the aqueous phase was extracted with ethyl acetate (3×100 mL). The combined extracts were washed with water, brine, dried over Na2SO4 and concentrated. The obtained dark brown residue was purified by column chromatography on silica gel (DCM:MeOH, 100:1 to 80:1) to afford 4 g of 1-(3-chloro-2-thienyl)-2-(pyridin-4-yl)ethanone (22% yield).

1. stirringThe reaction mixture was stirred at −50° C. for 30 min
2. temperatureto warm to room temperature
3. stirringstirred for 2 h
4. customThe mixture was quenched with aqueous saturated ammonium chloride solution (150 mL)
5. customThe organic layer was separated
6. extractionthe aqueous phase was extracted with ethyl acetate (3×100 mL)
7. washThe combined extracts were washed with water, brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated
10. customThe obtained dark brown residue was purified by column chromatography on silica gel (DCM:MeOH, 100:1 to 80:1)

ORD-Eintrag

ord-b669a51cbcc2415bb91d1caa29dfbb2e

Quelldatensatz

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08685974B2