Pyrrolo[2,1-c][1,4]benzoxazepines. 2. Synthesis of 5-phenyl derivatives

A series of 5-phenylpyrrolo2,1-c]1,4]benzoxazepines with basic substituents at the 11-position has been synthesized utilizing a nucleophilic aromatic fluoride displacement-cyclization. Piperidinyl derivatives were prepared by Vilsmeier formylation of the key 1-(2-fluorophenyl)phenylmethyl]pyrrole ( 4 ) followed by addition of a piperidinyl Grignard reagent and cyclization of the resulting carbinol. A (dimethylamino)methyl derivative was prepared via an analogous cyclization of α-(dimethylamino)methyl-1-(2-fluorophenyl)phenyl-methyl]-1H-pyrrole-2-methanol ( 10 ), obtained by the Hoeben-Hoesch acylation of 4 with chloroacetonitrile, addition of dimethylamine to the resulting α-chloroketone 8 , and reduction of the α-(dimethylamino)ketone 9 with sodium borohydride to give 10 .