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Spirodecanone

Spirodecanone refers to a class of spirocyclic ketones, often studied for their potential applications in medicinal chemistry. One notable example is 1-Phenyl-1,3,8-triazaspiro[4.5]decan-4-one, which has been investigated as a metabolite of neuroleptic agents like Fluspirilene. It has a molecular formula of and a melting point of 188-191 Ã‚°C.

Synthesis

The original synthesis was first disclosed by Paul Janssen, and was covered by Daniel Lednicer in one of his books.

A recent synthesis of spirodecanone is disclosed:

The Strecker-like condensation between N-benzyl-4-piperidone [3612-20-2] (1), aniline and TMSCN [7677-24-9], gives 4-anilino-1-benzylpiperidine-4-carbonitrile [968-86-5] (2). Acid catalyzed partial hydrolysis of the nitrile to the amide afforded 4-anilino-1-benzylpiperidine-4-carboxamide [1096-03-3] (3). Reaction with forms the spiroimidazolidone ring giving 8-benzyl-1-phenyl-1,3,8-triazaspiro[4.5]dec-2-en-4-one [974-42-5] (4). The imine bond is reduced with sodium borohydride giving 8-benzyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one [974-41-4] (5). Catalytic hydrogenation then removes the benzyl group (6).

It is noteworthy to mention that intermediate 4 finds dual use in the synthesis of some highly potent fentanyl analogs.

Applications

Listed in alphabetical order:

  1. DiPOA
  2. Fluspiperone is similar but with additional para-fluoro.
  3. Fluspirilene
  4. L008716
  5. Phencyclidine analog
  6. R-5260 [1109-69-9] (normethadone analog)
  7. R 6890 (spirochlorphine)
  8. RP-23618 [207991-30-8]
  9. Spiramide
  10. Spiroxatrine contains a Benzodioxan sidechain.
  11. Spirilene [357-66-4]
  12. Spiperone
  13. Ro64-6198 & Ro65-6570 (NOP receptor agonist).
  14. BRN 4620880 [99756-32-8]
  15. 8-(5,8-Dichloro-1,2,3,4-tetrahydro-2-naphthyl)-1-phenyl-1,3,8-triaza-spiro(4.5)decan-4-one.

References