产物官能团类型
1. 酰氯法
酸氯与胺反应生成酰胺是非常普遍的反应。通常，该反应在室温下进行，使用适当的碱（如 TEA 或 DIEA）在非质子溶剂（如 DCM、THF 或 DMF）中进行。
案例
To a stirring solution of the amine (100 mg, 0.236 mmol) in DCM (2 mL) at 0 C under N2 was added DIEA (0.203 mL, 1.18 mmol), followed by the acid chloride (88 mg, 0.471 mmol). The reaction mixture was stirred at RT for 16 h. The mixture was quenched with H2O and extracted with DCM. The org layer was washed with brine, dried (MgSO4), and concentrated in vacuo. The material was purified by Prep LC (12 g silica, 0-12% MeOH/DCM) to provide a white solid (83 mg). The material was purified by Reverse Phase chromatography to provide 55 mg of oil. The oil was diluted with ether and concentrated to provide the product as a waxy solid. [53 mg, 44%]
Patent Reference: WO2015144799, page 286
2.酰氯-胺两步法
从羧酸出发，通常采用两步法。首先使用亚硫酰氯（SOCl2）或草酰氯（(COCl)2）生成酸氯。粗酸氯被分离后，再按照上述类似方法与胺发生反应。
案例
SOCl2 (20 mL) was added to the SM (2.50 g, 8.47 mmol) and the mixture was refluxed for 16 h. The volatiles were removed in vacuo and the mixture was azeotroped with toluene (3 x 50 mL) to give a gum. To the crude mixture was added 2-methyl tetrahydrofuran (20 mL), followed by TEA (2.36 mL, 17 mmol) and the amine (907 mg, 10.2 mmol). The mixture was stirred at RT for 2 h, quenched with sat aq NaHCO3 (20 mL), and extracted with EtOAc (2 x 20 mL). The combined organics were washed with 10% aq citric acid (20 mL) and concentrated in vacuo to give a gum. The crude was triturated in ether to provide to product as a white solid. [2.32 g, 75%]
Patent Reference: WO2010032200, page 70