Novel Practical Deprotection of N-Boc Compounds Using Fluorinated Alcohols

Abstract

The thermolytic deprotection of N-Boc compounds was accomplished using TFE (2,2,2-trifluoroethanol) or HFIP (hexafluoroisopropanol) as solvents. Even though the cleavage of the t-butylcarbamate (Boc) group can be achieved at solvent reflux temperature, the deprotection process was significantly accelerated under microwave-assisted conditions. The practicality of this methodology was demonstrated on alkyl, aryl, and heteroaromatic N-Boc-amines.

Keywords:

• Boc-deprotection
• hexafluoroisopropanol
• microwave
• trifluoroethanol

ACKNOWLEDGMENT

The authors thank Joseph Muchowski, who suggested the use of HFIP as an alternative fluorinated solvent in this study. We also thank Yanzhou Liu and Kate Comstock for assistance in the analysis of all the compounds by NMR and HRMS.

Notes

^a Isolated yield after chromatography.

^a Isolated yields after chromatography.

^a Isolated yield after chromatography.

^a Isolated yields after chromatography.

^b At 150°C side products are formed and yield is low.

^c Crude yield (pure by NMR).