Improved method for the total synthesis of thiofentanyl

Thiofentanyl is a potent analgesic and anesthetic drug that belongs to the microreceptor agonist group and is mainly used in animal's anesthesia. We present an optimized synthesis route for synthesis of thiofentanyl using nanocatalysts such as MCM‐41‐SO3H and SBA‐15‐Ph‐PrSO3H as green, heteroge...

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Bibliographic Details
Published in:Journal of heterocyclic chemistry 2023-06, Vol.60 (6), p.950-956
Main Authors: Taghizadeh, M. J., Hosseini, S. J., Moosavi, S. M., Parsa, H.
Format: Article
Language:English
Subjects:
Alkylation
Anesthesia
Aniline
Chlorides
Functional groups
Phase transfer catalysts
Piperidine
Synthesis
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Summary:Thiofentanyl is a potent analgesic and anesthetic drug that belongs to the microreceptor agonist group and is mainly used in animal's anesthesia. We present an optimized synthesis route for synthesis of thiofentanyl using nanocatalysts such as MCM‐41‐SO3H and SBA‐15‐Ph‐PrSO3H as green, heterogeneous and recyclable catalysts according to the strategy. The intermediate 2‐(thiophen‐2‐yl) ethyl methanesulfonate (1) easily obtained after conversion of the alcohol functional group into the mesylate leaving group using methanesulfonyl chloride (97% yield). The alkylation of commercially available 4‐piperidone monohydrate hydrochloride with 2‐(thiophen‐2‐yl) ethyl methanesulfonate in the presence of phase transfer catalyst was then carried out giving N‐[2‐(2‐thienyl) ethyl]‐4‐piperidone (2) with 90% yield. N‐[2‐(2‐thienyl)ethyl]‐4‐piperidone was then reacted with aniline in the presence of MCM‐41‐SO3H catalyst giving the imine derivative which reduced with sodium triacetoxyborohydride to N‐phenyl‐1‐(2‐(thiophen‐2‐yl)ethyl) piperidine‐4‐amine (ANTP) (4) with 80% yield. ANTP was finally acylated using propionyl chloride to achieve thiofentanyl (5) with 90% yield. High yields, mild reaction conditions, decreased reaction times, and convenient workup were the advantages of this method compared to the previous work.
ISSN:0022-152X
1943-5193
DOI:10.1002/jhet.3983