The Synthesis of Octahydro-7-phenylpyrazino[2,1-b][3]benzazepines

Octahydro-7-phenylpyrazino[2,1-b][3]benzazepine ( 1a ) was prepared from 1-methyl-3-phenylmethylpiperazine 5a by reaction with styrene oxide followed by sulfuric acid cyclization of the resulting alcohol 6a . The diastereomeric mixture 1a was further separated into the diastereomers 1a′ and 1a″ . Similarly 1-methyl-3-(3-chloro-4-methoxyphenyl)piperazine was reacted with styrene oxide to yield 6c which on cyclization with 1.5 equivalents of sulfuric acid in trifluoroacetic acid gave a 3:7 mixture of phenolic, 1d , and methoxy, 1c , octa-hydropyrazino[2,1-b][3]benzazepines. The reaction of the 2,5-piperazinedione 4c with sodium acetoxyborohydride gave a 49% yield of the 2-piperazinone 7 which was similarly carried on to the corresponding 1(2H)-oxohexahydropyrazino[2,1-b][3]benzazepine 9 .