Synthesis
Michael addition of 3,4-dimethoxyphenylacetonitrile 17 to methyl acrylate 18 using
10% aq. NaOH under PTC conditions afforded double Michael adduct 19 in 75% yield.
Alternatively, compound 19 was obtained using catalytic Triton-B in refluxing CH3CN in
quantitative yields! Dieckmann condensation of 19 using NaH in DME furnished βketoester, which was demethoxycarbonylated using Krapcho’s method to obtain ketone 20.
Ketone 20 was protected as dioxolane with 2,2-dimethyl-1,3-propanediol in refluxing
benzene using PPTS as a catalyst.
Nitrile was then reduced with DIBAL in DCM at 0 o
C to obtain aldehyde, which
was converted to olefin 21 with methylenetriphenylphosphorane employing Wittig
reaction. Olefin 21 was then subjected to hydroboration with BMS complex, followed by
alkaline work-up to give alcohol, which was mesylated and the resultant mesylate was
further treated with 30% aq. MeNH2 solution in a sealed tube at 100 o
C to yield amine,
which was protected as benzyl carbamate. Dioxolane was then hydrolysed by refluxing in
an acetone-water mixture (1:1) with a drop of conc. H2SO4 to obtain ketone 22. Silyl enol
ether of the resultant ketone 22 was prepared, which was subsequently brominated with
NBS to give α-bromoketone, which upon dehydrobromination with LiBr and Li2CO3 in hot
DMF provided enone 23. The carbamate was unmasked with BF3·OEt2 in the presence of
excess of Me2S to give the target molecule 16 .
