A concise and regioselective synthesis of 6-iodo-4-trifluoromethylisatin, an intermediate in the synthesis of the novel, non-peptidyl growth hormone secretagogue SM-130686

The synthesis of 6-iodo-4-trifluoromethylisatin, an intermediate in the synthesis of the growth hormone secretagogue SM-130686, is disclosed. The synthesis is achieved in seven steps, with an overall yield of 32%, and requires a single recrystallisation as the only purification step. 2-Methyl-3-nitrobenzotrifluoride was converted to (4-iodo-6-nitro-2-trifluoromethylphenyl)acetic acid via iodination, condensation with dimethyloxalate and oxidative decarboxylation. Subsequent esterification followed by reductive cyclisation gave 6-iodo-4-trifluoromethyloxindole. Oxindole 3,3-dibromination followed by hydrolysis gave 6-iodo-4-trifluoromethylisatin.