Amide Coupling via a Mixed Anhydride Method

◆When R2=Piv the acylation product was 19, which was not able to be attacked by 4-nitrophenethylamine 15.

◆Considering that PivCl can act as a hydroxyl protective group, we proposed that adding excess PivCl might result in in situ protection of the hydroxyl group, followed by amidation.

◆A moderate conversion to product 10 was observed when 1.6eq of PivCl was added. However, byproduct 21 was also found in 8.2% conversion.

◆At first, it may seem that 21 was produced from 15 and excess PivCl.

◆However, only trace PivCl was detected by GC after refluxing in water implying 21 was formed via 20.

◆The only Lewis acid triethylamine hydrochloride came into view.

◆The triethylamine hydrochloride produced in the first step was removed by washing with water, and the triethylamine used as an acid scavenger in the successive acylation process was also avoided.