合成路线1

The building block (IX) can be obtained by several related methods:
Reaction of 4,4-dimethylcyclohexanone (XVII) with DMF and PBr3 under Vilsmeier formylation conditions provides the carbaldehyde (XVIII), which is subjected to reductive amination with 4-piperazinobenzoic acid ethyl ester (XIX) and NaBH3CN resulting in the cyclohexenylmethyl piperazine (XX). Subsequent Suzuki coupling of compound (XX) with 4-chlorophenylboronic acid (XXI) followed by ethyl ester hydrolysis of the resultant adduct (XXII) leads to the target intermediate (IX) (1). Scheme 3.
In a related procedure, 2-hydroxy-5,5-dimethyl-1-cyclohexenecarboxylic acid methyl ester (XXIII) is converted to the corresponding triflate (XXIV), which undergoes Suzuki coupling with boronic acid (XXI) to yield the 2-arylcyclohexenecarboxylate derivative (XXV). After reduction of ester (XXV) with LiBH4, the resulting primary alcohol (XXVI) is converted to the corresponding mesylate (XXVII) with methanesulfonyl chloride, and then condensed with the piperazine derivative (XIX) followed by ethyl ester hydrolysis to yield the key precursor (IX) (4). Scheme 3.