A general method for the separation of triphenylphosphine oxide and reaction products using high performance countercurrent chromatography

•A standardised HPCCC strategy was developed for removing TPPO from reaction mixtures.•Processing samples by uniform HPCCC conditions eliminated method development time.•A one column volume elution–extrusion method was used with TPPO eluting at D = 1.•Isolation of target ether from a set of crude Mitsunobu products was achieved.•Target purities and recoveries compared favourably to equivalent HPLC separations.

A standardised separation methodology was developed for the purification of crude reaction mixtures containing triphenylphosphine oxide (TPPO) using high performance countercurrent chromatography (HPCCC). A solvent system consisting of hexane/ethyl acetate/methanol/water (5:6:5:6) was used in 1 column volume elution–extrusion mode. The HPCCC methodology was compared with classical RP HPLC purification using a set of 12 representative Mitsunobu reaction mixtures. HPCCC was seen to yield a 65% increase in the average recovery of the target component whilst providing similar final target purities to those obtained by HPLC. By eliminating the need for method development for individual samples, the HPCCC methodology described within provides a simple and efficient means for the purification of the entire family of TPPO-containing reaction products.