Synthesis of key intermediate for (+)-tofacitinib through Co^III(salen)-catalyzed two stereocentered hydrolytic kinetic resolution of (±)-methyl-3-(oxiran-2-yl)butanoate

ABSTRACT

An enantiopure piperidine, a key intermediate for the synthesis of (+)-tofacitinib, has been achieved in high optical purity (98% ee) from readily available crotyl alcohol. The key steps involved is a Co^III(salen)-OAc-catalyzed two stereocentered hydrolytic kinetic resolution of (±)-methyl-3-(oxiran-2-yl)butanoate.

GRAPHICAL ABSTRACT

KEYWORDS:

• γ-Butyralactone
• enantioselective
• hydrolytic kinetic resolution
• iodolactonization

Acknowledgments

Rohit B. Kamble thanks CSIR (National Repository of Small Molecules) for providing fellowship and DST-SERB, New Delhi for funds. The authors are also thankful to Dr. S. S. Tambe, Chair, Chemical Engineering and Process Development Division for his constant encouragement and support.