Protection of 5-methoxyindole (I) with benzenesulfonyl chloride (II) in the presence of NaH affords the N-sulfonyl indole (III). Acylation of the 2-lithio derivative of (III) with benzoyl chloride (IV) gives rise to ketone (V). Finally, removal of the phenylsulfonyl protecting group of (V) is achieved by either basic hydrolysis or by treatment with tetrabutylammonium fluoride.
In a related method, the 2-lithio derivative of 5-methoxy-1-(phenylsulfonyl)indole (I) is condensed with benzaldehyde (II) to produce carbinol (III). Subsequent oxidation of (III) to the corresponding ketone (IV) is accomplished by treatment with pyridinium dichromate (PDC) in the presence of pyridinium trifluoroacetate (PTFA). Finally, the N-phenylsulfonyl group of (IV) is deprotected by treatment with tetrabutylammonium fluoride.
The alkaline hydrolysis of 5-methoxyisatin (I) provides the ortho-(aminophenyl)glyoxylic acid salt (II), which is then alkylated by 2-bromoacetophenone (III) to furnish the N-phenacylisatin (IV). Rearrangement of (IV) in the presence of NaOH gives rise to a 40:60 mixture of the indolecarboxylic acid (V) and the target decarboxylated compound.