Conjugate addition of the lithium enolate of ethyl 1,3-dithiolane-2-carboxylate (II) to methyl 3,4-dichlorocinnamate (I) afforded the diester adduct (III). Reduction of (III) with LiAlH4 gave diol (IV), which was selectively monosilylated with tert-butyldimethylsilyl chloride, yielding (V). Condensation of the potassium alkoxide of (V) with 3,5-bis(trifluoromethyl)benzyl bromide (VI) provided ether (VII). After desilylation of (VII) with HF in acetonitrile to alcohol (VIII), the hydrolysis of its thioketal function with mercuric perchlorate and CaCO3 furnished ketone (IX). Treatment of (IX) with methoxyamine gave rise to a mixture of (E)- and (Z)-oximes from which the desired (Z)-isomer (X) was isolated by flash chromatography. Swern oxidation of the alcohol functionality of (X) produced the corresponding aldehyde, which was reductively condensed with piperidinyl pyrrolidone (XI) in the presence of NaBH3CN to afford the title compound.

Conjugate addition of the lithium enolate of ethyl 1,3-dithiolane-2-carboxylate (II) to methyl 3,4-dichlorocinnamate (I) afforded the diester adduct (III). Reduction of (III) with LiAlH4 gave diol (IV), which was selectively monosilylated with tert-butyldimethylsilyl chloride, yielding (V). Condensation of the potassium alkoxide of (V) with 3,5-bis(trifluoromethyl)benzyl bromide (VI) provided ether (VII). After desilylation of (VII) with HF in acetonitrile to alcohol (VIII), the hydrolysis of its thioketal function with mercuric perchlorate and CaCO3 furnished ketone (IX). Treatment of (IX) with methoxyamine gave rise to a mixture of (E)- and (Z)-oximes from which the desired (Z)-isomer (X) was isolated by flash chromatography. Swern oxidation of the alcohol functionality of (X) produced the corresponding aldehyde, which was reductively condensed with piperidinyl pyrrolidone (XI) in the presence of NaBH3CN to afford the title compound.