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Furopyridines. VI. Preparation and reactions of 2‐ and 3‐substituted furo[2,3‐ b ]pyridines
Author(s) -
Morita Hiroyuki,
Shiotani Shunsaku
Publication year - 1986
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570230542
Subject(s) - chemistry , hydrolysis , ketone , pyridine , sodium borohydride , derivative (finance) , organic chemistry , medicinal chemistry , hydrazone , sodium ethoxide , formylation , alcohol , sodium cyanoborohydride , ethanol , catalysis , financial economics , economics
This paper describes the synthesis and chemical properties of some 2‐ and 3‐substituted furo[2,3‐ b ]pyridines. Reaction of ethyl 2‐chloronicotinate 1 with sodium ethoxycarbonylmethoxide or 1‐ethoxycarbonyl‐1‐ethoxide gave β‐keto ester 2 or ketone 5 , respectively. Ketonic hydrolysis of 2 afforded ketone 3, from which furo[2,3‐ b ]pyridine 4 was obtained by the method of Sliwa. While, 2‐methyl derivative 7 was prepared from 5 by reduction, O ‐acetylation and the subsequent pyrolysis. Reaction of ketone 3 with methyllithium gave tertiary alcohol 8 which was O ‐acetylated and pyrolyzed to give 3‐methyl derivative 9 . Formylation of 4 , via lithio intermediate, with DMF yielded 2‐formyl derivative 10 , from which 7 , was obtained by Wolff‐Kishner reduction. Dehydration of the oxime 11 of 10 gave 2‐cyano derivative 12 , which was hydrolyzed to give 2‐carboxylic acid 13 . Reaction of 3‐bromo compound 14 with copper(I) cyanide gave 3‐cyano derivative 15 . Alkaline hydrolysis of 15 afforded compound 16 and 17 , while acidic hydrolysis gave carboxamide 18 . Reduction of 15 with DIBAL‐H afforded 3‐formyl derivative 19 . Wolff‐Kishner reduction of 19 gave no reduction product 9 but hydrazone 20 . Reduction of tosylhydrazone 21 with sodium borohydride in methanol afforded 3‐methoxymethylfuro[2,3‐ b ]pyridine 22 .