A green and efficient monoacylation strategy for symmetrical diamines in microreactors†

Monoacylated diamines are common building blocks for numerous active pharmaceutical ingredients. However, the synthesis of these compounds often requires selective protection/deprotection steps, complex catalysts or harsh reaction conditions, leading to waste and poor atom economy. Here, we present a green and efficient procedure for the monoacylation of symmetrical diamines in a microreactor using acyl imidazole as an acyl donor. Taking the advantages of the microreactor, monoacylated diamines were synthesized with superior selectivity under mild conditions and short residence times. The wide substrate scope and selectivity of this continuous flow monoacylation process were confirmed through the synthesis of 20 pharmaceutically relevant amides. Moreover, the application of the monoacylation process in the preparation of antidepressant drug befuraline was achieved, demonstrating the value of this approach for pharmaceutical synthesis.