A Flow-Based Synthesis of 2-Aminoadamantane-2-carboxylic Acid

Abstract

The development of a new, high-yielding, scalable and safe process for the preparation of 2-aminoadamantane-2carboxylic acid (1) is described. This geminal, functionalized achiral amino acid has been reported to possess interesting biological activity as a transport mediator due to its unique physiochemical properties. We report herein on the use of various mesoreactor flow devices to expedite the lab-scale synthesis of this molecule by simplifying the processing requirements for use of several potentially hazardous reagent combinations and reaction conditions.

Flow chemistry approaches directed at improving chemical synthesis

“…It was discovered that when the dimethyll -tartrate and trimethyl orthoformate were premixed, rapid formation of an intermediate diacetal occurred, which was observed using the ReactIR flow cell ( Scheme 17 ). This proved to be an important observation and optimization of Guanadine library [80] Thiazole library [79] Oxazole library [83] Grossamide [81] Zolpidem [72] Meclinertant SR 48692 [74] Casein Kinase Inhibitors library [77] Aminopyrrolidines [78] Polypeptides [82] Scheme 15 A range of other targeted structures achieved using multi-step flow synthesis.…”

Flow Technology for Organometallic-Mediated Synthesis

“…Ley and coworkers developed an efficient, safe, and high-yielding flow process for preparing, even in large scale, 2-aminoadamantane-2-carboxylic acid using a continuous-flow reactor [45].…”

6.07 Ritter-Type Reactions

“…At 30°C the standard Ritter product was obtained in 91% yield, but substantial formation of the by-product occurred above 40°C. 49 Me 3 C-OH + NC-CH=CHCN …”