Improving the efficiency of solid phase peptide synthesis is important to meet the growing need for synthetic peptides. We have recently developed a new one-pot Fmoc SPPS process whereby the deprotection and coupling steps share the same solvent without any draining or delay between steps. This new process combined with microwave heating and optimized carbodiimide coupling reduces the entire cycle time to < 3 minutes (0.1mmol) while dramatically reducing overall waste generated. This method was further improved with the use of a greener solvent composition that maintained overall purity. Importantly, this mixture works well with widely used polystyrene resins and Fmoc amino acids thereby eliminating the need to use specialized reagents for compatibility.