Amidation of carboxylic acids via the mixed carbonic carboxylic anhydrides and its application to synthesis of antidepressant (1S,2R)-tranylcypromine
Primary amidations of carboxylic acids 1 or 3 with NH4Cl in the presence of ClCO2Et and Et3N were developed to afford the corresponding primary amides in 22% to quantitative yields. Additionally, we have applied the amidation to the preparation of various amides containing hydroxamic acids and achieved the synthesis of (1S,2R)-tranylcypromine as an antidepressant medicine via Lossen rearrangement.
Convenient preparation of primary amides via activation of carboxylic acids with ethyl chloroformate and triethylamine under mild conditions
Primary amides were easily prepared in 22-99% yields from the corresponding carboxylic acids 1 or 5 with NH4Cl via activation with ClCO 2Et and Et3N. The enantiomers of the corresponding primary amides of Cbz-, Boc-, or Fmoc-α-amino acids can be separated by using a chiral column.