US 12,145,919 B2
Method for preparing chiral synthetic nicotine
Jun Zou, Guangdong (CN); Yang Zou, Guangdong (CN); Meisen Liu, Guangdong (CN); and Weixian Luo, Guangdong (CN)
Assigned to SHENZHEN ZINWI BIO-TECH CO., LTD, Guangdong (CN)
Filed by SHENZHEN ZINWI BIO-TECH CO., LTD, Guangdong (CN)
Filed on Dec. 10, 2021, as Appl. No. 17/547,251.
Application 17/547,251 is a continuation of application No. PCT/CN2021/112799, filed on Aug. 16, 2021.
Claims priority of application No. 202110781304.6 (CN), filed on Jul. 10, 2021.
Prior Publication US 2023/0025652 A1, Jan. 26, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07B 53/00 (2006.01); C07D 401/04 (2006.01)
CPC C07D 401/04 (2013.01) [C07B 53/00 (2013.01)] 10 Claims
 
1. A method for preparing a chiral synthetic nicotine, comprising the following steps:
step S1, condensing nicotinic acid ester and γ-butyrolactone under an action of alkaline condensate in an organic solvent I to obtain a first mixture;
step S2, performing a ring-opening reaction to the first mixture obtained in the step S1 by adding an acidic substance to obtain a second mixture;
step S3, separating 4-chloro-1-(3-pyridine)-1-butanone from the second mixture obtained in the step S2, reacting 4-chloro-1-(3-pyridine)-1-butanone with a chiral tert-butyl sulfinamide in an organic solvent II and titanate to obtain a third mixture containing a chiral n-(4-chloro-1-(pyridin-3-yl)butene)-2-methylpropane-2-sulfinamide, filtering, extracting, and removing the organic solvent II to obtain a chiral n-(4-chloro-1-(pyridin-3-yl)butene)-2-methylpropane-2-sulfenamide;
step S4, dissolving the chiral n-(4-chloro-1-(pyridin-3-yl)butene)-2-methylpropane-2-sulfenamide obtained in the step S3 in an organic solvent III, reacting with a reducing agent, and then cyclizing under an action of hydrogen halide to obtain a fourth mixture; and
step S5, reacting the fourth mixture obtained in the step S4 with a methylamination reagent to obtain a fifth mixture, and purifying the fifth mixture to obtain the chiral synthetic nicotine.