PyBOP

This coupling reagent does not release carcinogenic by-products and can be used in place of BOP reagent in most applications. It is soluble in a range of solvents, including THF, CH2Cl2, DMF, and NMP. Solutions of this reagent are stable for approximately 24 hours and should be prepared fresh daily.

Coupling with Benzotriazole-1-yloxy-tris-pyrrolidinophosphonium Hexafluorophosphate

1. Remove the N-protecting group using standard deprotection protocols. 

2. Dissolve 1.1 equivalents (based on resin substitution) of the protected amino acid in DMF (5 mL/g of resin) and add to the resin. 

3. Add 1.1 equivalents (based on resin substitution) of 1.0 M PyBOP solution and 2.2 equivalents (based on resin substitution) of diisoproplyethylamine (DIPEA). 1.1 equivalents (based on resin substitution) of 0.5 M HOBt solution in DMF can be added to suppress racemization.

 4. Mix for 10-60 minutes until the Kaiser test is negative.