Acid-Amine Coupling using Mukaiyama Reagent

Acid-Amine Coupling by Mukaiyama reagent;

General Procedure:

To a solution of acid (1 eq.) in DCM (10 Vol) is added 2-Chloro-1-methylpyridinium iodide (Mukaiyama reagent, 2.5 eq) at 0 °C and stirred for 30 min. To this reaction mixture at 0 °C, amine (1.2 eq.) in DCM (5 Vol) and DIPEA (1.2 eq) are added. The reaction is then brought to RT and stirred overnight. The reaction is monitored by TLC. The organic layer is diluted with CH₂Cl₂ (10 Vol) and then successively washed with water (15 ml x 2) and brine solution (15 ml). The resultant organic layer is dried using sodium sulphate, filtered and concentrated under reduced pressure. The crude product is purified by column chromatography.

Note:

• 2-Chloro-1-methylpyridinium iodide is known as Mukaiyama reagent

• The most preferable solvent is DCM.

For more details on reactions and reagents, 
refer to the tab "Reaction, Reagents and Mechanism"

Typical Procedure:

• Amidation of carboxylic acids using 2-Chloro-1-methylpyridinium iodide (Mukaiyama’s reagent) (ChemSpider) — Open access

• Peptide Coupling using Mukaiyama Condensation Reagent (TCI) — Open access

For more details on large-scale reactions and OPRD procedures, 
refer to the tab "Scale-up & Green Chem"

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