With a feasible synthetic plan in hand, we set out to prepare the fragments using solid phase peptide synthesis (Scheme 1). The Tau(1-40) sequence 3 terminated with MeNBz was synthesized on the Fmoc-MeDbz-Rink Amide Chem-Matrix resin but conversion into the N-acylurea (Nbz) thioester surrogate was unsuccessful because the peptide underwent oxidation, carbonylation, and dehydration upon treatment with the activating reagent (p-NO2C6H4OCOCl). We reasoned that the sheer length of the peptide fragment may be the source of this instability. Therefore, we dissected 3 into two smaller units Tau (1-14) and Tau (15-40), which both could be easily prepared by SPPS. Activation of the truncated peptides A15C-D40 5a did not suppress decomposition, and neither did bulky Mpe derivative (Mpe = 3-(3-methyl)pentyl ester), and only the N-terminal fragment M1-H14 could be efficiently converted into activated acyl donor MeDbz 4.