2-Fluoropyridine → 2-Methyl-1-(pyridin-2-yl)-1H-benzimidazole

Temperature

100 °C

To a stirred solution of 2-methyl-1H-benzimidazole (6.61 g, 50 mmol) in dimethylacetamide (40 ml) at room temperature under a nitrogen atmosphere was added sodium hydride (2.40 g, 60 mmol) in portions during 15 min. At the point where the reaction mixture was too viscous to stir, the reaction was diluted with 100 ml of dimethylacetamide. After 50 min., a solution of 2-fluoropyridine (5.83 g, 60 mmol) in dimethylacetamide (30 ml) was added during 15 min. The resulting mixture was heated at 100° C. for 2 h and then to reflux for about 4 h. Volatiles were removed by evaporation under reduced pressure. The residue was dissolved into ethyl acetate (200 ml) and washed consecutively with water (3×100 ml) and brine (100 ml). The organic layer was dried (magnesium sulfate) and concentrated to dryness. Purification by column chromatography (silica gel, 300 g; n-hexane/ethyl acetate (17/3)) yielded 7.46 g (71%) of the titled compound as a light yellow liquid. 1H-NMR (CDCl3) δ: 8.72-8.67 (1H, m), 7.95 (1H, ddd, J=7.7, 7.7, 1.8 Hz), 7.78-7.74 (1H, m), 7.49-7.36 (3H, m), 7.32-7.20 (2H, m), 2.69 (3H, s).

1. temperatureto reflux for about 4 h
2. customVolatiles were removed by evaporation under reduced pressure
3. dissolutionThe residue was dissolved into ethyl acetate (200 ml)
4. washwashed consecutively with water (3×100 ml) and brine (100 ml)
5. dry with materialThe organic layer was dried (magnesium sulfate)
6. concentrationconcentrated to dryness
7. customPurification by column chromatography (silica gel, 300 g; n-hexane/ethyl acetate (17/3))

ORD record

ord-e3afa1e531c442fe976e5b9318187d1d

Source dataset

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06713482B2