Improved Process for the Preparation of 6-Chloro-5-(2-chloroethyl)oxindole

The current process for ziprasidone involves preparation and isolation of the key intermediate 6-chloro-5-(2-chloroethyl)oxindole. An improved process for the synthesis of this intermediate is reported here. The new process involves use of a novel Lewis acid-mediated selective deoxygenation of the precursor ketone with tetramethyldisiloxane. The new method affords the desired compound in a one-pot process obviating the need for isolation of the potentially hazardous precursor ketone. This process was successfully scaled up to multikilo scale.