We report on a large-scale synthesis of F-PNA trimer 10 and PNA trimer 11. The key improvement is the facile two-step synthesis of (2,4-difluoro-5-methylphenyl)acetic acid (2). Water solubility of the corresponding F-PNA oligomer 10 was achieved by synthesizing solubility enhancer 5a, which is twofold positively charged and only consists of inherent structural elements of PNA. Protected and unpaired PNA n-mers exist in a mixture of 2 n conformers undergoing slow exchange and leading to complicated NMR spectra. Structure analysis was improved by recording 1 H-and 13 C-NMR spectra at elevated temperatures above the coalescence point. Fully protected backbone derivatives show sharp resonances where expected, and spectra of protected PNAs are remarkably simplified, thereby allowing an interpretation for the first time. Both trimers 10 and 11 are considered as building blocks for a selfreplicating system based on PNA.