API isolation
End of reaction mixture was treated with sodium phosphate and filtered to obtain a homogenous solution with 55-63% purity as analyzed using a liquid chromatography method with liquid chromatography area percentage (LCAP). The homogeneous solution was then mixed with 18 wt% sodium carbonate and a phase cut was performed to obtain a homogenous solution with 70-80% LCAP. A pH swing recrystallization was then performed to obtain the free acid form with >99% LCAP (Figure 1a). A process change from tandem reactions to one pot reaction was later developed and the API was purified utilizing organic extraction after Na2HPO4 treatment and filtration to extract MK-1454 API into organic phase followed by several aqueous washes and back-extraction of the API into the aqueous phase with the addition of NaOH solution. The pH was then neutralized by the addition of HCl solution to crystallize the API (Figure 1b).