Sodium hydride → 4-((2,3-Dimethyl-4-nitrophenoxy)methyl)pyridin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (2-aminopyridin-4-yl)methanol (1.33 g, 10.8 mmol) in DMF (10 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 537 mg, 13.4 mmol) and the reaction mixture maintained at 0° C. for 5 min and then warmed to RT for 1 hr. The mixture was re-cooled to 0° C., treated with a solution of 1-fluoro-2,3-dimethyl-4-nitrobenzene (2.00 g, 12.0 mmol) in DMF (5.0 mL) and after 2 min was warmed to RT. After 20 hr the reaction mixture was diluted with saturated aq. NH4Cl (50 mL) and extracted with EtOAc (2×100 mL) and then ether (100 mL). The combined organic extracts were dried and evaporated in vacuo to afford a red oil. The residue was diluted with acetonitrile (50 mL), upon which a brown precipitate formed. The precipitate was removed by filtration and the filtrate was evaporated in vacuo. This residue was purified by flash column chromatography (SiO2, 80 g, MeOH in DCM, 0-5%, gradient elution) to afford the title compound, Intermediate C3, as a yellow solid (1.19 g, 39%); Rt 1.35 (Method 2); m/z 274 (M+H)+ (ES+).

Provenance & Evidence