Preparation of (R)-3-hydroxy-n-methylpiperidine, a synthetic key intermediate of (R)-mepenzolate, based on the lipase-catalyzed resolution of the racemic form

Yasunobu Yamashita, Kengo Hanaya, Mitsuru Shoji, Takeshi Sugai

Research output: Contribution to journalArticle

Abstract

In this study, a two-step method for the gram-scale synthesis of (R)-3-hydroxy-N-methylpiperidine in 97.8% enantiomeric excess (ee) is reported. The key chiral synthetic intermediate of (R)-mepenzolate was formed in 22% yield over two steps using a commercially available and inexpensive racemic alcohol as the starting material. In the first step, Candida antarctica lipase B-catalyzed kinetic resolution of the racemic alcohol under acetylation conditions was performed to obtain the acetate form of the (R)-enantiomer in 82.1% ee (E 18). The second step involved enantio-enrichment using the same lipase to catalyze deacetylation. The ee of the product (R)-alcohol was further enriched to 97.8%.

Original languageEnglish
Pages (from-to)370-379
Number of pages10
JournalHeterocycles
Volume95
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

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Lipase
Alcohols
Acetylation
Enantiomers
Acetates
Kinetics
mepenzolic acid

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmacology
  • Organic Chemistry

Cite this

Preparation of (R)-3-hydroxy-n-methylpiperidine, a synthetic key intermediate of (R)-mepenzolate, based on the lipase-catalyzed resolution of the racemic form. / Yamashita, Yasunobu; Hanaya, Kengo; Shoji, Mitsuru; Sugai, Takeshi.

In: Heterocycles, Vol. 95, No. 1, 01.01.2017, p. 370-379.

Research output: Contribution to journalArticle

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