Kilogram Synthesis of (S)-3-Aminopyran from l-Glutamic Acid

We describe the development of a concise route to prepare kilogram quantities of ( S )-3-aminopyran, a key intermediate in the synthesis of a Jak1 inhibitor. The chiral amine was introduced via a chiral-pool approach and involves using inexpensive, commercially available l -glutamic acid as the key starting material. Global protection, followed by reduction afforded the N -Boc-amino diol. Intramolecular Mitsunobu cyclization and deprotection afforded the desired compound in 30% overall yield over four steps without the use of chromatography.