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

• Published in: Journal of heterocyclic chemistry Vol. 28; no. 5; pp. 1219 - 1224
• Main Authors: Ohnmacht Jr, Cyrus J., Mclaren, Frances M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley-Blackwell 01-08-1991; Wiley‐Blackwell; HeteroCorporation
• Subjects: Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Organic chemistry; Preparations and properties; Aromatic compound; Tetracyclic compound; Cyclization; Angular nitrogen heterocycle; Diastereomer
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.5570280511

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.