2-Chlorotrityl Chloride and 4-Methylbenzhydryl Bromide Resin Loading Using the Mixture of Organic Solvents: A “Greener” Alternative to Dichloromethane andN,N-Dimethylformamide

Common protocols for the loading of 2-CTC and MBH-Br resins presume the application of DCM, THF, or DMF; these solvents are considered as undesirable in accordance with modern regulatory rules. An alternative option implies the usage of rather expensive 2-MeTHF. Herein, we describe the application of an EtOAc/AcN (1:1) mixture as an efficient solvent alternative for the incorporation of the first amino acid. We show that the suggested reaction conditions ensure a loading level comparable to the usage of DCM, THF, 2-MeTHF, and DMF. The described procedure was designed for the kilogram-scale synthesis of a palmitoyl-hexapeptide.