ARS | Publication request: Improved preparation of haloalkyl bridged carboxylic ortho esters

Submitted to: Meeting Abstract
Publication Type: Abstract
Publication Acceptance Date: August 21, 2008
Publication Date: August 17, 2008
Citation: Petroski, R.J. 2008. Improved preparation of haloalkyl bridged carboxylic ortho esters [abstract]. 236th American Chemical Society Meeting Abstracts. p. 74.

Technical Abstract: Protection of a carboxylic acid function as a bridged ortho ester derivative enables the use of strong basic conditions in the synthetic strategy. For example, a protected 3-halopropionic acid can behave like an alkyl halide because the protons, alpha to the halide function, are less acidic. Esterification of 3-methyl-3-hydroxyoxetane with 3-bromopropionyl chloride and pyridine in dry tetrahydrofuran, followed by rearrangement with boron trifluoroetherate, afforded 1-(2-bromoethyl)-4-methyl-2,6,7-triazabicyclo[2,2,2]-octane. The 1-(2-iodoethyl)-4-methyl-2,6,7-triazabicyclo[2,2,2]-octane analogue could not be prepared directly by halogen exchange of 1-(2-bromoethyl)-4-methyl-2,6,7-triazabicyclo[2,2,2]-octane but could be prepared by halogen exchange of the 3-bromopropionate ester of 3-methyl-3-hydroxyoxetane with a mixture of sodium iodide and anhydrous sodium sulfate in acetone, followed by rearrangement with boron trifluoroetherate.