Study on the Lithiation Reaction of 3-Diisopropylcarbamoyl-N-pivaloylphenylethylamine

Abstract

As a continuation of our earlier studies on the lithiation-based synthesis of 8-methoxy-, 8-fluoro- and 8-chloro-3,4-dihydroisoquinoline, a similar approach was investigated for the preparation of the 8-diisopropylcarbamoyl congener. The corresponding N-pivaloyl phenylethylamine key intermediate was prepared via four new bifunctional intermediates in high overall yield. Lithiation of this intermediate followed by quenching with dimethylformamide led to a mixture: beside the desired compound containing the formyl moiety in the common ortho position of the two aromatic substituents, the isomer formylated in the other ortho position of the carbamoyl moiety was surprisingly obtained as the major product. The crude mixture could finally be transformed under acidic conditions to the target compound, 8-diisopropylcarbamoyl-substituted 3,4-dihydroisoquinoline, albeit in a low yield.