Abstract
A straightforward approach for the synthesis of several new, aryl-substituted derivatives of the conformationally constrained phenylalanine analogue 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) is described. Tic, nitro-substituted at the 6 or 7 position, was prepared by base-catalyzed cyclization of diethyl acetamidomalonate with α,α-dibromo-4-nitro-o- xylene followed by decarboxylation and deacylation under refluxing conditions in aqueous HCl. Catalytic hydrogenation of nitro-Tic in the presence of 10% Pd/C afforded amino-Tic, which was then converted to iodo-Tic by a modified Sandmeyer reaction. Both amino- Tic and iodo-Tic can easily be transformed to other substituents.
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Ma, W., Mosberg, H.I. Synthesis of 6- or 7-substituted 1,2,3,4-tetrahydroisoquinoline- 3-carboxylic acids. Letters in Peptide Science 6, 179–183 (1999). https://doi.org/10.1023/A:1008826909441
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DOI: https://doi.org/10.1023/A:1008826909441