Efficient synthesis of [6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]-acetic acid, a novel COX-2 inhibitor

The synthesis of 6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-ylacetic acid (1), a selective cyclooxygenase 2 (COX-2) inhibitor, is described. The synthesis relied on a novel indole formation that involved an alkylation/1,4-addition/ elimination/isomerization cascade. It was demonstrated that the entire sequence from sulfonamide 13 and bromoketone 14 to the desired indole (1) could be executed in a single pot.