Continuous and convergent access to vicinyl amino alcohols

Area of Science:

• Organic Chemistry
• Chemical Synthesis
• Process Chemistry

Background:

• The vicinyl amino alcohol moiety is a key structural feature in many active pharmaceutical ingredients (APIs).
• Traditional synthesis methods can be lengthy and inefficient for producing complex molecules.

Purpose of the Study:

• To develop a novel, continuous flow system for the synthesis of APIs containing the vicinyl amino alcohol moiety.
• To demonstrate the system's capability in producing two distinct classes of beta-amino alcohols.

Main Methods:

• A convergent chemical assembly system utilizing four integrated flow reaction modules was employed.
• The modules included biphasic oxidation, Corey-Chaykovsky epoxidation, phenol alkylation, and epoxide aminolysis.
• Strategic selection of reagents and module sequencing was critical for successful synthesis.

Main Results:

• Five active pharmaceutical ingredients (APIs) were successfully synthesized.
• The continuous flow system yielded good overall product yields ranging from 27% to 69%.
• Two classes of beta-amino alcohols, specifically aryl and aryloxy types, were produced.

Conclusions:

• The developed continuous flow system offers an efficient and effective approach for synthesizing vicinyl amino alcohol-containing APIs.
• This methodology enables the streamlined production of diverse beta-amino alcohol structures.
• The system's modularity and strategic reagent/module selection are key to its success.