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

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.

Comparison of preparative reversed phase liquid chromatography and countercurrent chromatography for the kilogram scale purification of crude spinetoram insecticide.

Reversed phase HPLC (RP-HPLC) and high performance countercurrent chromatography (HPCCC) were compared for the pilot scale purification of two semi-synthetic spinosyns, spinetoram-J and spinetoram-L, the major components of the commercial insecticide spinetoram. Two, independently performed, 1 kg, purification campaigns were compared. Each method resulted in the isolation of both components at a purity of >97% and yields for spinetoram-J and spinetoram-L of >93% and ≥ 63% of theoretical, respectively. The HPCCC process produced a 2-fold higher throughput and consumed approximately 70% less solvent than preparative scale RP-HPLC, the volume of product containing fractions from HPCCC amounted to 7% of that produced by HPLC and so required much less post-run processing.