A simple and convenient TeflonTM-based method for N-methyltetrapeptide purification relying on fluorous 9-fluorenylmethanol as a C-terminal protecting group was developed. Fluorous compound–protected peptides supported on TeflonTM powder could be easily transferred between the fluorous solid phase (TeflonTM) and the liquid phase (reaction solution) by tuning the hydrophobicity of the solvent. Fluorous peptides present in a homogeneous state in solution during each elongation reaction were immobilized on TeflonTM at the end of each reaction by adjusting the hydrophobicity of the reaction solution, and they could be isolated by simple filtration, affording the facile synthesis of the corresponding N-methylated tetrapeptide.