It can clearly be seen that the structure is based on
dichloroisoprenaline that has been fused onto the bicycloalkane scaffold.
Synthesis
An intramolecular
Dieckmann cyclization on methyl 4-(2-methoxy-2-oxoethyl)cyclohexanecarboxylate [1401222-79-4] (3) with sodium hydride base gives reaction Methyl 3-oxobicyclo[2.2.2]octane-2-carboxylate [30144-30-0] (4). Treatment with
sodium nitrite introduces an isonitroso group adjacent to the ketone, giving 3-Hydroxyiminobicyclo[2.2.2]octan-2-one,
CID:131066320 (5). Addition of the aryl Grignard reagent, and reduction of the oxime gives
CID:154108204 (6). A reductive amination of the primary amino group with acetone then completed the synthesis of cilobamine (7).
^Leeson GA, Shaath ZA, Biedenbach SA, Yarrington JT, Okerholm RA (April 1984). "Dose related induction of the drug metabolizing enzymes of rat liver by cilobamine". Fundamental and Applied Toxicology. 4 (2 Pt 1): 261–9.
doi:
10.1016/0272-0590(84)90127-1.
PMID6724198.
^Wager S, Quitkin F, Stewart J, McGrath P, Harrison W, Markowitz J, Tricamo E (1988). "Cilobamine in the treatment of atypical depression". Human Psychopharmacology: Clinical and Experimental. 3 (3): 201–205.
doi:
10.1002/hup.470030308.
S2CID145253439.