Convenient, Large-Scale Synthesis of (S)-TRIP Using Suzuki Cross-Coupling Conditions

A three-step synthesis of ( S )-TRIP enabled by efficient Suzuki cross-coupling conditions using commercial starting materials was developed and demonstrated on a kilogram scale. These novel Suzuki reaction conditions feature Pd 2 (dba) 3 /CataCXium A in the presence of TBAB and KOH and provide conversions up to 90% while minimizing the formation of common byproducts. Following an improved demethylation protocol and a powerful methanol purification protocol during step 2, high-quality catalyst of up to 99% purity was isolated in 52% yield over three steps.