The synthesis, purification, and use of N-(2-acetoxy-4-methoxybenzyl)(AcHmb) backbone amide protected segments in the preparation of Asp(158)-Leu(251) from the 3-repeat region of human tau-2 has been investigated. Fmoc/tert-butyl based(1,2) fully protected segments of 9-21 residues, containing appropriately placed AcHmb protection were prepared on Polyhipe SU500 resin through a 2-chlorotrityl linker. Protected segments, cleaved with 0.75% trifluoroacetic acid in dichloromethane, were easily purified in 100s of milligram quantities by either silica gel chromatography or standard aqueous acetonitrile based reverse phase preparative HPLC. Purified protected segments, typically soluble at >500 mg mL(-1) in dimethylformamide, coupled efficiently and economically to a growing resin-bound assembly, to give the 94-mer human tau-2 with an overall purified yield of 2.50 mu mol (16.7%).