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.