在NMI存在下，TCFH会迅速转化为中间体ii，ii和羧酸反应生成酰基咪唑鎓盐iii，由于酰基咪唑鎓盐iii活性极高，会迅速和胺反应得到酰胺。按照此反应历程，至少需要两个当量的NMI，反应才能顺利进行。

生成酰基咪唑鎓盐iii的过程和HATU酰胺化机理类似。

对于一些反应活性很低的胺作为底物进行反应，发现在室温下进行也可以得到很高的产率。

General Procedure 1. N-(4-cyanophenyl)-2-methyl-2-phenylpropanamide (3a): The 2-methyl-2- phenylpropanoic acid 1 (0.250 g, 1.52 mmol, 1.0 equiv), 0.234 g 4-aminobenzonitrile (2a) (1.98 mmol, 1.3 equiv) and 0.42 mL N-methylimidazole (5.33 mmol, 3.5 equiv) were combined and dissolved in 4 mL MeCN for addition of 0.517 g TCFH (1.83 mmol, 1.2 equiv) in a single portion. The reaction was stirred until complete by HPLC (21h). The reaction was then diluted with 6 mL of isopropyl acetate and 4 mL of water. The s were separated, the aqueous was extracted with 4 mL of isopropyl acetate and the combined organics were washed with 4 mL of water, dried with MgSO4, filtered and concentrated before purification by silica gel chromatography with heptane/isopropyl acetate to give 374 mg of 3a as a white solid (93% yield).2 In some cases, direct isolation of the desired amide could be achieved through addition of 4-6 mL water, filtration and washing with 5 mL of 2:1 water/MeCN before drying under nitrogen without a significant change in yield. Reported yields represent those obtained by chromatography for consistency. TLC Rf = 0.38 (7:3 heptane/isopropyl acetate, UV 254 nm).

但是对于α-位有手性中心的羧酸，NMI的量太多会发生消旋。

因此得到优化的反应条件：TCFH(1.1 eq），NMI(2.1eq），乙腈，23℃