A method for the quantification of resin loading using 19F gel phase NMR spectroscopy and a new method for benzyl ether linker cleavage in solid phase chemistry

A simple and efficient method for monitoring and quantifying the extent of loading onto polymer resin supports for solid-phase synthesis using 19F gel-phase NMR spectroscopy is described. This assay was utilised in the synthesis of an inositol monophosphatase inhibitor on Merrifield resin. A series of Merrifield resin derived benzylic ethers were prepared and were cleaved from the resin when treated with SnCl4 at room temperature to give the expected alcohol, phenol or olefin. This new cleavage method was used to remove the inositol monophosphatase inhibitor from the resin. A method for quantifying polymer support loading, using 19F gel phase NMR spectroscopy and a facile method for the cleavage of Merrifield resin derivatives is described in the context of a solid phase synthesis of phosphatase inhibitor 6