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 language | English |
|---|---|
| Pages (from-to) | 370-379 |
| Number of pages | 10 |
| Journal | Heterocycles |
| Volume | 95 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2017 Jan 1 |
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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 journal › Article
}
TY - JOUR
T1 - Preparation of (R)-3-hydroxy-n-methylpiperidine, a synthetic key intermediate of (R)-mepenzolate, based on the lipase-catalyzed resolution of the racemic form
AU - Yamashita, Yasunobu
AU - Hanaya, Kengo
AU - Shoji, Mitsuru
AU - Sugai, Takeshi
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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%.
AB - 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%.
UR - http://www.scopus.com/inward/record.url?scp=85065604277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065604277&partnerID=8YFLogxK
U2 - 10.3987/COM-16-S(S)28
DO - 10.3987/COM-16-S(S)28
M3 - Article
VL - 95
SP - 370
EP - 379
JO - Heterocycles
JF - Heterocycles
SN - 0385-5414
IS - 1
ER -