A comparative study of modern coupling reactions involving Boc‐protected amino acid derivatives and dipeptides withN‐terminal α,α–dialkylation andN‐methylation was carried out. The coupling reactions were run using either equimolar amounts of the amino and activated carboxyl components or an excess of the activated carboxyl component. Yields of the target tripeptide Boc‐Phe‐Xaa‐Phe‐OBzl (Xaa = (NMe)Ala, (NMe)Alb, or (NMe)αAc5c) were compared. Less than 10% of the product was obtained from methods utilizing pivaloyl mixed anhydride, pentafluorophenyl ester or acyl fluoride activation when Xaa = (NMe)Aib and (NMe)αcAc5c. At room temperature, significant yields of these two products were obtained from reactions which utilized an excess of the HBTU reagent (O‐benzotriazol‐1‐yl‐N,N,N′,N′‐tetramethyluronium hexafluorophosphate), the PyBroP reagent (bromo‐tris‐pyrrolidino‐phosphonium hexafluorophosphate) or Boc‐Phe‐NCA (Boc‐protected phenylalanineN‐carboxyanhydride). Moreover, the Boc‐Phe‐NCA method was superior when used over a