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

Temperature

25 °C

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].

1. waitAfter 3 h the reaction mixture was transferred to a sealed flask
2. stirringwas stirred at 130° C. for 18 h
3. stirringthe reaction was stirred at 130° C. for another 36 h
4. stirringthe mixture stirred at 140° C. for 6 h
5. waitat 130° C. for 18 h
6. temperatureThe mixture was cooled
7. concentrationconcentrated onto silica gel
8. custompurified by chromatography (silica, Analogix 120 g, 0 to 100% ethyl acetate in hexanes, 60 min)

ORD record

ord-77efc71dd7ad451aade3771ff793c515

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901124B2