Concise synthesis of 3,7-dioxa-9-aza-bicyclo[3,3,1]-nonane.
[reaction: see text] The basicity of an amine has a great impact on physicochemical properties and pharmacokinetics. To attenuate the basicity of morpholine, a bicyclic amine was designed and synthesized with the introduction of an additional beta-oxygen. A transannular cyclization and reduction of a bridgehead alpha-chloro amine functionality produces the topographically unusual amine (pKa = 6.7) in good yield.
Park
Cheol-Min
CM
Cancer Research, Global Pharmaceutical R&D, Abbott Laboratories, 100 Abbott Park Rd., Abbott Park, Illinois 60064, USA. cheol-min.park@abbott.com
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
C511883:3,7-dioxa-9-aza-bicyclo(3,3,1)-nonane; D000473:Alkanes; D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; C017573:nonane