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[摘要]：2-Methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile is a key intermediate in the synthesis of selective androgen receptor modulators discovered in these laboratories. A practical and convergent synthesis of the title compound starting from 4-nitro-3-(trifluoromethyl) phenol and tert-butyl acetoacetate was developed, including a telescoped procedure for synthesis (without isolation) and Nenitzescu reaction of 2-trifluoromethyl-1,4-benzoquinone. Conversion of the known Nenitzescu indole product to a novel triflate intermediate followed by palladium-catalyzed cyanation afforded a penultimate carbonitrile. Removal of the C-3 tert-butyl ester group on the indole through a decarboxylative pathway completed the synthesis of the title compound in six steps (27% overall yield) from 4-nitro-3-(trifluoromethyl)phenol (five steps, 37% overall yield from tert-butyl acetoacetate). |
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