Chiral Pool Synthesis of N-Cbz-cis-(3R,4R)-3-methylamino-4-methylpiperidine from L-Malic acid

Abstract

A new synthetic route to N-Cbz-cis-(3R,4R)-3-methylamino-4-methylpiperidine, key intermediate for CP-690,550, was disclosed with L-malic acid as the chiral pool starting material. The title compound was obtained in 16 steps with a total yield of 26% and more than 98% ee.

Tofacitinib Synthesis – An Asymmetric Challenge

“…An alternative method employs l ‐malic acid ( 45 ) as the chiral pool starting material, to attain the Cbz‐protected compound 52 (Scheme ) . Despite the extensive synthetic sequence (16 steps), the authors claim that the synthetic sequence possessed several advantages, such as cheap raw materials, mild reaction conditions and an overall yield of 26 % yielding the product 54 with > 98 % ee .…”