Short and Scalable Synthesis of Enantiopure N-Boc-trans-4-methyl-L-prolinol

A scalable and chromatography-free synthesis of enantiopure N-Boc-trans-4-methyl-l-prolinol (1) on the multi-gram scale is described. Two shortest possible routes have been developed using commercially available and inexpensive amino acids such as 4-hydroxy-l-proline and l-pyroglutamic acid to afford 1 (>99% purity by high-performance liquid chromatography) with a moderate yield. This chiral precursor can act as a promising building block by providing practical access to a diverse array of 4-alkyl-l-prolines.