The recent explosive growth in the number of oligonucleotide clinical development programs and drug approvals underscores their ability to treat diseases via mRNA regulation. Currently, solid-supported synthesis is limited to ≤ 5 kg (~ 1 mole) batch sizes and the feasibility of liquid-phase syntheses to supply materials of sufficient purity and amount for clinical trials has not been proven. Herein we describe the first convergent synthesis of a full-length 18-mer mixed backbone (PO/PS) 2’-MOE gapmer oligonucleotide by the phosphoramidite approach suitable for use in clinical trials. Techniques described to control impurities during its synthesis can be implemented in common active pharmaceutical ingredient (API) manufacturing facilities and should enable a >10-fold increase in production batch scaling.