TDBTU

TDBTU is a coupling reagent that causes very little epimerization. In the coupling of peptide fragments to form SK&F 107647, TDBTU was shown to produce significantly less epimerization than PyBOP, HBTU, HATU, and many other common coupling reagents.1 TDBTU was utilized in the large scale synthesis of over 2 kg of SK&F 107647.1 Fragment Coupling1 

1. Dissolve the peptide ester in DMF (N,N-dimethylformamide) (approximately 16 ml per mmole of peptide ester).

 2. Add 1.25 equivalents of of the N-protected peptide fragment. 

3. Cool the solution to -25˚ C. 

4. Add 2.25 equivalents of DIEA (diisopropylethylamine).

 5. Add 1.05 equivalents of TDBTU. 

6. Stir at –25˚ C for one hour. 

7. Stir overnight at room temperature 

8. Pour the mixture into water (10 times the volume of DMF) containing 8% w/w sodum carbonate.

 9. Stir for 30 minutes 

10. Collect the solid by filtration, wash with water, and dry in vacuo to obtain the crude product.