A micro-flow rapid dual activation approach for urethane-protected α-amino acid -carboxyanhydride synthesis.

This study demonstrated the rapid dual activation (10 s, 20 °C) of a combination of an α-amino acid -carboxyanhydride and alkyl chloroformate in the synthesis of a urethane-protected α-amino acid -carboxyanhydride in a micro-flow reactor. The key to success was the combined use of two amines that activated both substrates with proper timing. Three amines, -PrNEt, MeNBn, or -ethylmorpholine, were used with pyridine in accordance with the steric bulkiness of a side chain in the α-amino acid -carboxyanhydride.