4383-26-0Relevant articles and documents
Preparation method of medical intermediate N-BOC-3-pyrroline
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Paragraph 0065-0066; 0069-0070; 0073-0074, (2021/07/31)
The invention discloses a preparation method of a medical intermediate N-BOC-3-pyrroline. The method comprises the following steps: adding a proper amount of benzylamine, 3-bromopropylene, dichloromethane and an alkaline reagent into a reaction bottle for reaction to obtain an enamine compound; dissolving the enamine compound in dichloromethane, adding a catalyst (Grubbs first generation) for reaction, adding anhydrous sodium sulfate after adding water for layering, and performing suction filtration to obtain mother liquor; adding 1-chloroethyl chloroformate and methanol into the mother liquor, debenzylating to obtain pink solid, adding petroleum ether into the pink solid, pulping, and carrying out suction filtration to obtain 3-pyrroline hydrochloride; and re-dissolving the 3-pyrroline hydrochloride with water, adding an alkaline solution of NaHCO3 and (BOC)2O, stirring and reacting, extracting after the reaction is finished, separating out an organic phase, and drying to obtain a finished product of N-BOC-3-pyrroline. The method is low in raw material cost, simple in process step, high in yield, small in pollution, high in product purity and suitable for industrial production.
A Simple, Broad-Scope Nickel(0) Precatalyst System for the Direct Amination of Allyl Alcohols
Sweeney, Joseph B.,Ball, Anthony K.,Lawrence, Philippa A.,Sinclair, Mackenzie C.,Smith, Luke J.
supporting information, p. 10202 - 10206 (2018/08/06)
The preparation of allylic amines is traditionally accomplished by reactions of amines with reactive electrophiles, such as allylic halides, sulfonates, or oxyphosphonium species; such methods involve hazardous reagents, generate stoichiometric waste streams, and often suffer from side reactions (such as overalkylation). We report here the first broad-scope nickel-catalysed direct amination of allyl alcohols: An inexpensive NiII/Zn couple enables the allylation of primary, secondary, and electron-deficient amines without the need for glove-box techniques. Under mild conditions, primary and secondary aliphatic amines react smoothly with a range of allyl alcohols, giving secondary and tertiary amines efficiently. This “totally catalytic” method can also be applied to electron-deficient nitrogen nucleophiles; the practicality of the process was demonstrated in an efficient, gram-scale preparation of the calcium antagonist drug substance flunarizine (Sibelium).
Direct use of allylic alcohols and allylic amines in palladium-catalyzed allylic amination
Jing, Jiangyan,Huo, Xiaohong,Shen, Jiefeng,Fu, Jingke,Meng, Qinghua,Zhang, Wanbin
supporting information, p. 5151 - 5154 (2017/07/12)
Allylic alcohols and allylic amines were directly utilized in a Pd-catalyzed hydrogen-bond-activated allylic amination under mild reaction conditions in the absence of any additives. The cooperative action of a Pd-catalyst and a hydrogen-bonding solvent is most likely responsible for its high reactivity. The catalytic system is compatible with a variety of functional groups and can be used to prepare a wide range of linear allylic amines in good to excellent yields. Furthermore, this methodology can be easily applied to the one-step synthesis of two drugs, cinnarizine and naftifine, on a gram scale.
