Catalytic direct amidations in tert-butyl acetate using B(OCH₂CF₃)₃

Area of Science:

• Organic Chemistry
• Green Chemistry
• Medicinal Chemistry

Background:

• Catalytic direct amidation is crucial for pharmaceutical synthesis.
• Current methods often use unsustainable non-polar solvents.
• These solvents limit the use of polar substrates common in medicinal chemistry.

Purpose of the Study:

• To develop a sustainable catalytic direct amidation reaction.
• To improve substrate scope for polar and functionalized compounds.
• To enhance the utility of amidation in medicinal chemistry.

Main Methods:

• Utilized tert-butyl acetate as a reaction solvent.
• Employed a catalytic system for direct amidation.
• Scaled up the reaction to 100 mmol.

Main Results:

• Achieved a practical and useful catalytic direct amidation.
• Demonstrated improved reaction scope with polar substrates and less nucleophilic anilines.
• Scaled-up reaction showed excellent yield and efficiency (PMI of 8).

Conclusions:

• Tert-butyl acetate offers a safer and more sustainable solvent alternative.
• The developed method expands the applicability of catalytic amidation for medicinal chemistry.
• The reaction is efficient, scalable, and suitable for synthesizing complex amides.