An integrated five-step continuous flow synthesis of 2-(1-cyclohexenyl)ethylamine: a key intermediate for morphinans

Abstract

Morphinans are highly pharmacologically active chemicals and widely used as analgesic and antitussive agents in clinical treatment. 2-(1-Cyclohexenyl)ethylamine is an important intermediate to construct a series of morphinans. Herein, a continuous flow synthesis of 2-(1-cyclohexenyl)ethylamine was developed starting from cyclohexanone via five chemical transformations. This work features an expeditious synthesis of 2-(1-cyclohexenyl)ethylamine in an integrated flow platform with in-line separation and without any intermediate purification. The overall yield of this multi-step flow method was up to 56% in a total residence time of 44.5 min, corresponding to a throughput of 32 mmol h⁻¹.