Bridged-ring nitrogen compounds. Part 10. Synthesis of bridged 3-benzazepine derivatives as conformationally restricted dopamine analogues

Abstract

Ethyl 3,4-dimethoxyphenyl(phenyl)acetate 7, (R = Et), made by an improved procedure, was converted into ethyl 1,2,3,4-tetrahydro-6,7-dimethoxy-4-oxo-1-phenyl naphtha lene-1-ca rboxylate 15 which was used both in a synthesis of 2,3,4,5-tetra hydro-7,8-dihydroxy-1-phenyl-1,4-methano-1H-3-benzazepine and as starting material for 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1,4-ethano-1H-3-benzazepine 4via ethyl 1,2,3,4-tetrahydro-6,7-dimethoxy-4-methylene-1-phenylnaphthalene-1-carboxylate 16 and ethyl 6,7,8,9-tetrahydro-2,3-dimethoxy-8-oxo-5-phenyl-5H-benzocycloheptene-5-carboxylate 33. The compound 16 was converted into ethyl 1,2,3,4-tetra hydro-4-hydroxymethyl-6,7-dimethoxy-1-phenylnaphthalene-1-carboxylate 18, (X = OH) which could not be converted into derivatives of 1,5-ethano-3-benzazepine. Ethyl α-(3,4-dimethoxyphenyl)phenyl acetate was converted in three steps into 6,7,8,9-tetrahydro-2,3-dimethoxy-9-phenyl-6,9-methano-5H-benzocycloheptene-5,10-dione 10(R′= Ph, R²= R³= OMe) which was selectively reduced and aminated giving 6,7,8,9-tetrahydro-2,3-dihydroxy-9-phenyl-6,9-methano-5H-benzocyclohepten-10-amine 6 hydrobromide.