Title:
PREPARATION METHOD FOR SYNTHESIZING S-NICOTINE FROM GLUTARIC ACID ESTER
Document Type and Number:
WIPO Patent Application WO/2023/284059
Kind Code:
A1
Abstract:
A preparation method for synthesizing S-nicotine from glutaric acid ester: nicotinic acid ester and glutaric acid ester are used to react under the action of a basic catalyst to obtain 5-carbonyl-5-(pyridin-3-yl)valeric acid; then, 5-carbonyl-5-(pyridin-3-yl)valeric acid is subject to a reaction with an amination reagent to obtain 5-oxo-5-(pyridin-3-yl)pentanamide; then, 5-oxo-5-(pyridin-3-yl)pentanamide is subject to Hoffmann rearrangement to obtain 4-amino-1-(pyridin-3-yl)butanone, and a carbonyl group of 4-amino-1-(pyridin-3-yl)butanone is reduced by using (+)-B- pinocampheyl chloroborane to obtain (S)-4-amino-1-(pyridin-3-yl)butan-1-ol; then, (S)-4-amino-1-(pyridin-3-yl)butan-1-ol is subject to chloro-ring closure to obtain S-desmethylnicotine; and finally S-desmethylnicotine is subject to amine methylation to obtain S-nicotine. The described method has the advantages of simple operations, easily available raw materials, high yield, a high ee value, etc., and has mild reaction conditions and simple treatment procedures for the reaction process, which is more suitable for industrial production.
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Inventors:
ZOU JUN (CN)
ZOU YANG (CN)
LIU MEISEN (CN)
LUO WEIXIAN (CN)
ZOU YANG (CN)
LIU MEISEN (CN)
LUO WEIXIAN (CN)
Application Number:
PCT/CN2021/112805
Publication Date:
January 19, 2023
Filing Date:
August 16, 2021
Export Citation:
Assignee:
SHENZHEN ZINWI BIO TECH CO LTD (CN)
International Classes:
C07D401/04
Foreign References:
| CN104341390A | 2015-02-11 | |||
| CN104341390A | 2015-02-11 | |||
| CN11233829A |
Other References:
HUANG KUN, ORTIZ-MARCIALES MARGARITA, DE JESúS MELVIN, STEPANENKO VIATCHESLAV: "A new and efficient approach to the synthesis of nicotine and anabasine analogues", JOURNAL OF HETEROCYCLIC CHEMISTRY, WILEY-BLACKWELL PUBLISHING, INC., US, vol. 46, no. 6, 1 November 2009 (2009-11-01), US , pages 1252 - 1258, XP093022372, ISSN: 0022-152X, DOI: 10.1002/jhet.233
FELPIN, F. X. ET AL.: "Efficient Enantiomeric Synthesis of Pyrrolidine and Piperidine Alkaloids from Tobacco", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 66, no. 19, 23 August 2001 (2001-08-23), pages 6305 - 6312, XP002647122, DOI: 10.1021/jo010386b
GUARNA, A. ET AL.: "Baker's Yeast Reduction of Prochiral gamma-Nitroketones: Enantioselective Synthesis of (S)-4-Nitroalcohols", TETRAHEDRON, vol. 51, no. 6, 31 December 1995 (1995-12-31), pages 1775 - 1788, XP004104864, DOI: 10.1016/0040-4020(94)01056-6
YE JIAN-LIANG, ZHANG YU-FENG, LIU YANG, ZHANG JIN-YUAN, RUAN YUAN-PING, HUANG PEI-QIANG: "Studies on the asymmetric synthesis of pandamarilactonines: an unexpected syn-selective vinylogous Mannich reaction of N-tert-butanesulfinimines", ORGANIC CHEMISTRY FRONTIERS, vol. 2, no. 6, 1 January 2015 (2015-01-01), pages 697 - 704, XP093022373, DOI: 10.1039/C5QO00098J
JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 46, no. 6, 2009, pages 1252 - 1258
FELPIN, F. X. ET AL.: "Efficient Enantiomeric Synthesis of Pyrrolidine and Piperidine Alkaloids from Tobacco", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 66, no. 19, 23 August 2001 (2001-08-23), pages 6305 - 6312, XP002647122, DOI: 10.1021/jo010386b
GUARNA, A. ET AL.: "Baker's Yeast Reduction of Prochiral gamma-Nitroketones: Enantioselective Synthesis of (S)-4-Nitroalcohols", TETRAHEDRON, vol. 51, no. 6, 31 December 1995 (1995-12-31), pages 1775 - 1788, XP004104864, DOI: 10.1016/0040-4020(94)01056-6
YE JIAN-LIANG, ZHANG YU-FENG, LIU YANG, ZHANG JIN-YUAN, RUAN YUAN-PING, HUANG PEI-QIANG: "Studies on the asymmetric synthesis of pandamarilactonines: an unexpected syn-selective vinylogous Mannich reaction of N-tert-butanesulfinimines", ORGANIC CHEMISTRY FRONTIERS, vol. 2, no. 6, 1 January 2015 (2015-01-01), pages 697 - 704, XP093022373, DOI: 10.1039/C5QO00098J
JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 46, no. 6, 2009, pages 1252 - 1258
Attorney, Agent or Firm:
BEIJING WEIZHENG PATENT AGENCY CO., LTD. (CN)
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