反应详情

A mixture of 3-methyl-pyrazine-2-carboxylic acid ethyl ester (Example 1.1) (0.5 g), N-bromosuccinimide (“NBS”) (0.536 g) and 2,2′-azobis(2-methylpropionitrile) (“AIBN”) (0.487 g) in carbon tetrachloride (2.5 ml) was heated to reflux. After 1 hour thin layer chromatography showed a mixture of starting material and the desired product. Further NBS (0.536 g) and AIBN (0.243 g) were added and the reaction mixture heated for a further 1 hour. The percentage of product increased and impurities began to form. The reaction mixture was cooled to ambient temperature and then to 0° C. The cold mixture was filtered and the filtrate concentrated. The residue was purified by chromatography on silica gel (eluent: 0-10% v/v ethyl acetate in iso-hexane) to give 3-bromomethyl-pyrazine-2-carboxylic acid ethyl ester (640 mg) contaminated with 3-methyl-pyrazine-2-carboxylic acid ethyl ester (due to co-elution, ˜3:2). MH+=245, RT=1.26 min (Method A).

1. temperaturewas heated to reflux
2. additiona mixture of starting material