BOP (Castro’s Reagent)

BOP reagent is a coupling reagent which suppresses racemization during coupling reactions. It is useful in difficult couplings where standard symmetrical acid anhydride and HOBt activated chemistries fail to give good results. This reagent must be used and handled with caution. Hexamethylphsophotriamide (HMPA), a carcinogen, is formed as a by-product when BOP is used. To avoid this hazard, bezotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate can be used in place of BOP reagent. Wear safety goggles, chemical resistant gloves, and protective clothing when using BOP reagent. Do not breath the dust from this product. Clean up any spills immediately and dispose of the spilled material in an appropriate chemical waste container.

 Coupling with BOP Reagent

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

2. Dissolve 2.0 equivalents (based on resin substitution) of the protected amino acid in DMF (5 mL/g of resin) and add to the resin.

 3. Add 2.0 equivalents (based on resin substitution) of 1.0 M BOP solution and 4.0 equivalents (based on resin substitution) of diisopropylethylamine (DIPEA). 2.0 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