Synthesis of 3-Methyl-5,6-dihydro-3H-benzofuroisoquinolin-7(7aH)-ones

Article abstract of DOI:10.1021/jo00172a032

The coupling of 2-(alkoxymethoxy)phenylcopper derivatives with the salt of ethyl chloroformate and ethyl 3-(pyridin-3-yl)propenoate was found to be an efficient method for the preparation of 4-(2-hydroxyphenyl)pyridines 13 substituted at C-3 with a propanoate side chain.N-Methylation and O-alkylation with ethyl bromoacetate gave salts 3 which when treated with base underwent an intramolecular enolate addition to the pyridinium nucleus to produce spiro 4.Prolonged base treatment of 4 yielded ethyl 3-methyl-7-hydroxy-5,7a-dihydro-3H-benzofuro<3,2-e>isoquinoline-6-carboxylates 5 by a Dieckmann reaction.Reduction of 5 led to predominately trans-3-methylhexahydro-1H-benzofuro<3,2-e>isoquinolin-7(7aH)-ones, while reduction of 4 and then Dieckmann cyclization yielded mainly the cis isomers.