%0 Journal Article
%T Synthesis and Molecular Structure of tert-Butyl 3-oxo-2-oxa-5-azabicyclo[2.2.2]octane-5-carboxylate
%A Tetsuji Moriguchi
%A Suvratha Krishnamurthy
%A Toru Arai
%A Taisuke Matsumoto
%A Koji Araki
%A Akihiko Tsuge
%A Norikazu Nishino
%J Journal of Crystallography
%D 2014
%R 10.1155/2014/645079
%X The compound tert-butyl 3-oxo-2-oxa-5-azabicyclo[2.2.2]octane-5-carboxylate was synthesized as a cyclic amino acid ester from the corresponding ethyl 2-amino-4-(2-oxiranyl)butanoate HCl salt via an intramolecular lactonization reaction and was characterized by using 1H NMR spectroscopy and high-resolution mass spectrometry. The product was then recrystallized from dichloromethane/diethyl ether and its structure was determined via single crystal X-ray diffraction analysis. The crystal was found to be of the monoclinic space group P21/c (no. 14) with £¿£¿, £¿£¿, £¿£¿, ¦Â = 114.186(13)¡ã, and = 1.350£¿g/cm3 at 123£¿K. The compound has bicyclo[2.2.2]octane structure including a lactone moiety and a piperidine ring, and the two diastereomers of the molecules are present in a 1£¿:£¿1 ratio in the crystal. 1. Introduction The compound hydroxypipecolic acid (5-hydroxy-2-piperidinecarboxylic acid) is a six-membered homologue of 4-hydroxyproline. Hydroxypipecolic acid is found in some natural plants such as date and acacia trees, whereas 4-hydroxyproline is found in animals (collagen) [1, 2]. Several hydroxypipecolic acid derivatives have been synthesized via the intramolecular reactions of precursors functionalized with epoxide groups [3¨C5]. Generally, a diastereomeric mixture of cis- and trans-5-hydroxymethylpipecolic acids has been obtained. The formation of 5-hydroxymethylprolines along with the desired 5-hydroxypipecolic acids has also been noted [4¨C6]. The intramolecular reaction from epoxide precursor suffers the formation of both stereoisomers (cis and trans) and regioisomers (pipecolic acid and proline). The synthetic reports so far seem to be confused because of the formation of many products. The straightforward method to isolate this rare amino acid, hydroxypipecolic acid, is still desired with a clear compound characterization. Previously, we synthesized a 4-hydroxyproline derivative from an amino acid bearing epoxide [7]. During this study, we observed that the cis isomer underwent intramolecular lactonization. Then, the product lactone, tert-butyl 3-oxo-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxylate, was isolated from the trans ester with ease. It was expected that cis-5-hydroxypipecolic acids would also undergo intramolecular lactonization, whereas the trans isomers would not. Indeed, when a mixture of cis- and trans-5-hydroxypipecolic acids derivatives reacted under acidic conditions, the cis isomer was successfully converted to the lactone, tert-butyl 3-oxo-2-oxa-5-azabicyclo[2.2.2]octane-5-carboxylate, which was readily separated from the remaining
%U http://www.hindawi.com/journals/jcrys/2014/645079/