Method of asymmetrically synthesizing nicotine
AssigneeShenzhen Catalys Technology Co., Ltd
InventorsShuang GAO, Qiwei LANG, Xiaobing DING
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Abstract
A method for preparing nicotine. (1) The nicotinic acid alkyl ester and N-methylpyrrolidone are subjected to a condensation reaction, and then added with a strong acid to obtain 4-methylamino-1-(3-pyridine)-butanone hydrochloride. (2) The 4-methylamino-1-(3-pyridine)-butanone hydrochloride is reacted with an amino-protecting reagent to obtain an intermediate (4). (3) A chiral alcohol (5) is obtained through an asymmetric reduction. (4) The chiral alcohol (5) is converted into the nicotine through a two-step reaction.
Claims10
A method for preparing an intermediate of formula (5) in the preparation of nicotine, comprising:
- subjecting compound (4) to asymmetric reduction in the presence of a catalyst to produce the intermediate (5), as shown in the following reaction scheme:
- wherein R2 is selected from the group consisting of C1-2 alkyl, heteroatom-substituted alkyl, aryl and amino-protecting group;
- the catalyst is prepared through complexation of a metal salt with a chiral ligand;
- the metal salt is an inorganic salt of a transition element selected from the group consisting of ruthenium, rhodium, iridium and palladium and the chiral ligand is selected from the group consisting of:
A compound of formula (4) or formula (5):
- wherein R2 is selected from the group consisting of C1-2 alkyl, heteroatom-substituted alkyl, aryl and an amino-protecting group;
- the amino-protecting group is selected from the group consisting of benzyloxycarbonyl (Cbz), tert-butoxycarbonyl (Boc), fluorenylmethyloxycarbonyl (Fmoc), allyloxycarbonyl (Alloc), (trimethylsilyl)ethoxycarbonyl (Teoc), methoxycarbonyl, ethoxycarbonyl, phthaloyl (Pht), p-toluenesulfonyl (Ts), trifluoroacetyl (Tfa), nitrobenzenesulfonyl (Ns), pivaloyl, benzoyl, trityl (Trt), 2,4-dimethoxybenzyl (Dmb), p-methoxybenzyl (PMB) and benzyl (Bn);
- and the compound of formula (5) is R or S configuration.
Dependencies are inferred from the claim text.