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.
Key words
aminopyran - Mitsunobu - intramolecular - cyclization - glutamic acid - chiral pool - diols
