2-Amino-6-chloropyridine → 6-Ethoxy-2-pyridinamine

Participants

Reaction Conditions

Reaction Steps

In a vial in a water bath, a 21% wt solution of sodium ethoxide in ethanol (1.08 g, 1.25 mL, 15.9 mmol) was diluted in ethanol (4 mL) and stirred at 25° C. for 10 min then 6-chloropyridin-2-amine (2.0 g, 15.6 mmol) was added in a single portion. After 3 h the reaction mixture was transferred to a sealed flask and was stirred at 130° C. for 18 h. A second portion of 21% wt solution of sodium ethoxide in ethanol (1.08 g, 1.25 mL, 15.9 mmol) was added and the reaction was stirred at 130° C. for another 36 h. Finally, a third portion of a 21% wt solution of sodium ethoxide in ethanol (3.18 g, 3.66 mL, 46.7 mmol) was added and the mixture stirred at 140° C. for 6 h then at 130° C. for 18 h. The mixture was cooled, concentrated onto silica gel, and purified by chromatography (silica, Analogix 120 g, 0 to 100% ethyl acetate in hexanes, 60 min) to give 6-ethoxypyridin-2-amine (819 mg, 36%) that was used directly without further purification. MS (EI/CI) m/z: 139 [M+H].

Provenance & Evidence