Efficient Fmoc Group Removal Using Diluted 4-Methylpiperidine: An Alternative for a Less-Polluting SPPS-Fmoc/tBu Protocol

4-methylpiperidine is a toxic substance and is harmful to people and the environment. This reagent is commonly used for Fmoc group removal in SPPS-Fmoc/tBu, and this reaction is carried out using 4-methylpiperidine in DMF (20–25% v/v). We tested the efficiency of using diluted solutions of 4-methylpiperidine for SPPS-Fmoc/tBu. Fmoc removal was complete (> 99%) using 2.5% 4-methylpiperidine. The use of a diluted Fmoc removal reagent allowed us to synthesize peptides containing from 6 to 20 amino acid residues, with high purity and good yield. This process is less harmful for the environment and for humans, and furthermore it is less expensive.