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

A convenient synthesis of furo[3,2-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-hydroxyfuro[3,2-b]pyridine-2-carboxylate (3) which in turn was hydrolyzed and decarboxylated to give furo[3,2-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 furo[3,2-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-methylfuro[3,2-b]pyridine-2-carboxylic acid (10). Decarboxylation of 10 afforded 3-methylfuro[3,2-b]pyridine (11).