Asymmetric synthesis of (R)-6-amino-1-methyl-4-(3-methyl-benzyl)hexahydro-1H-1,4-diazepine from L-asparagine

✍ Scribed by Shiro Kato; Hiroshi Harada; Toshiya Mode

• Book ID: 102892813
• Publisher: Journal of Heterocyclic Chemistry
• Year: 1997
• Tongue: English
• Weight: 772 KB
• Volume: 34
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570340516

✦ Synopsis

Abstract

An efficient asymmetric synthesis of (R)‐6‐amino‐1‐methyl‐4‐(3‐rnethylbenzyl)hexahydro‐1__H__‐1,4‐diazepine [(R)‐2] which serves as the amine part of (R)‐1, a potent and selective 5‐HT~3~ receptor antagonist, is described. Formation of the hexahydro‐1__H__‐1,4‐diazepine ring was achieved by the intramolecular ami‐dation of the optically active aminocarboxylic acid 18 or reductive cyclization of the optically active aminoaldehyde 25. Compounds 18 and 25 were prepared from L‐asparagine via the key aziridine derivatives 15 and 22, respectively, with retention of the configuration. The intramolecular aziridine ring opening reaction of 29 gave the C~2~N bond cleavage product of the aziridine ring, the piperazin‐5‐one 30, as the main product along with the desired 7‐membered ring, the hexahydro‐1__H__‐1,4‐diazepine product 19.