PyBrOP

This reagent is recommended for coupling hindered amino acids. It has proven effective for coupling N-methylamino acids whereas many other reagents are ineffective or impractical. When used with dimethylaminopyridine (DMAP), it is effective for coupling alpha-methyl amino acids such as α-aminoisobutyric acid. 

Coupling N-Methyl Amino Acids with Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate(PyBrOP )

1. Remove the N-protecting group from the resin peptide using standard procedures. 

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

3. Dissolve 2 equivalents (based on resin substitution) of the protected amino acid in DCM or DMF. Add the solution to the resin. 

4. Add 2 equivalents (based on resin substitution) of PyBroP® . Cool the mixture to 0 °C. 

5. Add 6 equivalents of diisopropylethylamine (DIPEA). Mix 1 minute cold and 1 hour at room temperature.

 6. Filter the resin and wash with DCM.