DIC(Diisopropylcarbodiimide )

Diisopropylcarbodiimide (DIC) is a coupling reagent used to form amides and esters. Since the diisopropylurea, which forms as a byproduct, is soluble in organic solvents and remains in solution under most reaction conditions, DIC is used in solid phase chemistry to couple compounds to resin supports or resinsupported products. In forming esters and thioesters from acids and alcohols, addition of a catalytic amount of 4-(N,N-dimethylamino)pyridine (DMAP) greatly enhances the rate of reaction. When DIC is used in peptide coupling, 1-hydroxybenzotriazole  is added to suppress racemization. DIC is a sensitizer and can cause chemical burns. Wear safety goggles, chemical resistant gloves, and protective garments when using DCC. 

Coupling on Resins 

1. Remove the N-protecting group using standard procedures. 

2. Suspend the resin in DCM or DMF (approximately 10 mL/gram resin).

 3. Dissolve 2.5 equivalents (based on resin substitution) of the protected amino acid and 2.5 equivalents of HOBt in a minimum amount of DMF. Add this solution to the resin. 

4. Add 2.5 equivalents of diisopropylcarbodiimide (DIC). Shake the mixture under an inert atmosphere for 3-6 hours. The reaction can be monitored with the Kaiser test.

 5. After the reaction is complete, wash the resin with DMF and DCM.