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Synthesis of 7‐azabicyclo[2.2.1]heptane derivatives by transformation of tropinone
Author(s) -
GómezSénchez Elena,
MarcoContelles José
Publication year - 2006
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570430607
Subject(s) - chemistry , octane , yield (engineering) , halogenation , heptane , bicyclic molecule , carboxylate , organic chemistry , stereochemistry , medicinal chemistry , metallurgy , materials science
The bromination (CuBr 2 , AcOEt/CHCI 3 ) plus Favorskii rearrangement (EtONa, EtOH) of N ‐carbethoxytropinone ( 4 ), readily available from tropinone ( 3 ), affords mixtures of exo ‐ and endo ‐isomers of 2,7‐dicarbethoxy‐7‐azabicyclo[2.2.1]heptane ( 1b ) in variable and moderate chemical yield (maximum 37%). The bromination (Br 2 , HBr/AcOH) reaction of compound 4 gives ethyl trans ‐2,4‐dibromo‐3‐oxo‐8‐azabicyclo[3.2.1]octane‐8‐carboxylate ( 5 ) in 99% yield, a product that on Favorskii rearrangement (EtONa/EtOH) affords ethyl 2,2‐diethoxy‐3‐oxo‐8‐azabicyclo[3.2.1]octane‐8‐carboxylate in moderate yield ( 6 ) (52%).