AbstractPeptide nucleic acids (PNA) were synthesized by a modified Merrifield method using several improvements. Activation by O‐(benzotriazol‐1‐yl)‐1,1,3,3‐tetramethyluronium hexafluorophosphate in combination with in situ neutralization of the resin allowed efficient coupling of all four Boc‐protected PNA monomers within 30 min. HPLC analysis of the crude product obtained from a fully automated synthesis of the model PNA oligomer H‐CGGACTAAGTCCATTGC‐Gly‐NH2, indicated an average yield per synthetic cycle of 97.1%. N1‐benzyloxycarbonyl‐N63‐methylimidazole triflate substantially outperformed acetic anhydride as a capping reagent. The resin‐bound PNAs were successfully cleaved by the ‘low–high’ trifluoromethanesulphonic acid procedure.