Highly efficient procedures were developed for greener synthesis of sequence-defined peptoid oligomers. The optimised chain elongation procedure is carried out in water-based media in a unique N to C direction, and comprises a convenient one-pot two-step deprotection/coupling sequence for the installation of each new peptoid residue. The process is so efficient that the only work-up procedure required after each intermediate coupling step is aqueous extraction. In stark contrast to the traditional procedures, the only solvents apart from water used during the synthesis and workup processes are EtOH, MeOH or EtOAc. Furthermore, there is no requirement for specialised water-soluble protecting groups or inclusion of additives apart from the reagents in the reaction media.