Furopyridines. III. A new synthesis of furo[3,2-b]pyridine

A convenient synthesis of furo3,2-b]pyridine and its 2- and 3-methyl derivatives from ethyl 3-hydroxypiconate ( 1 ) is described. The hydroxy ester 1 was O-alkylated with ethyl bromoacetate or ethyl 2-bromopropionate to give the diester 2a or 2b . Cyclization of compound 2a afforded ethyl 3-hydroxyfuro3,2-b]pyridine-2-carboxylate ( 3 ) which in turn was hydrolyzed and decarboxylated to give furo3,2-b]pyridin-3-(2H)-one ( 4a ). Cyclization of 2b gave the 2-methyl derivative 4b . Reduction of 4a and 4b with sodium borohydride yielded the corresponding hydroxy derivative 5a and 5b respectively, which were dehydrated with phosphoric acid to give furo3,2-b]pyridine ( 6a ) and its 2-methyl derivative ( 6b ). 2-Acetylpyridin-3-ol ( 8 ) was converted to the ethoxycarbonylmethyl ether ( 9 ) by O-alkylation with ethyl bromoacetate, which was cyclized to give 3-methylfuro3,2-b]pyridine-2-carboxylic acid ( 10 ). Decarboxylation of 10 afforded 3-methylfuro3,2-b]pyridine ( 11 ).