Acid-Amine Coupling using T3P

Acid-Amine Coupling by T3P;

General Procedure:

To a solution of acid (1 eq.), amine (1 eq.), and DIPEA or Et₃N (3 eq) in CH₂Cl₂ (10 Vol) at 0 °C is added T3P (50% in EtOAc, 2 eq) slowly over a period of 30 min. 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 10 % citric acid (10 Vol), water (5 Vol x 2), NaHCO₃ solution and brine solution. The resultant organic layer is dried using sodium sulphate, filtered and concentrated under reduced pressure. The crude product is purified by column chromatography.

Note:

• T3P is 1-Propanephosphonic acid cyclic anhydride (PPAA). It usually comes as 50 % solution in organic solvents such as EtOAc, DMF or acetonitrile

• The most preferable solvent is DCM. Other solvents are DMF

• T3P is a trade name.

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

Typical Procedure:

• Condensation of piperidine with N-protected phenylalanine (ChemSpider) — Open access

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

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