Fluorenylmethoxycarbonyl-N-methylamino Acids Synthesized in a Flow Tube-in-Tube Reactor with a Liquid-Liquid Semipermeable Membrane

Both steps of the N-methylation of 9-fluorenylmethoxycarbonyl (Fmoc) amino acids were carried out in a microstructured tube-in-tube reactor equipped with a semipermeable Teflon((R)) AF 2400 membrane as the inner tubing. In the first step, gaseous formaldehyde was passed through the inner membrane to effect the acid-catalyzed conversion of the Fmoc amino acids into the corresponding N-Fmoc oxazolidinones. In the second step, liquid-liquid transfer of trifluoroacetic acid was used for the first time in such a reactor for the reductive opening of these oxazolidinones to give Fmoc N-methylamino acids in high yields.