Sertraline, Pfizer process

One of the most widely used methods to improve overall process efficiency is to reduce the number of steps and unit operations in a synthetic route. This is more commonly known as telescoping. This can lead to more efficient, less wasteful processes that require fewer solvents because of the smaller number of steps. An example of this technique was illustrated earlier in Section 3.1.6, where the process optimization of the sertraline (Zoloft ) production process by Pfizer was described. In this case the number of process steps (unit operations) was reduced from 3 to 1, which led to huge savings due to higher productivity, fewer inputs, and less waste generation [18]. 

Sertraline is the active pharmaceutical ingredient (API) in Pfizer s antidepressant Zoloft [25]. The developed commercial process employs an SMB chromatographic resolution of tetralone (Scheme 13.10) in >99% ee followed by diastereoselective reductive amination to give 95% sertraline (cis-isomer) and 5% trans-isomer the (4R)-tetralone can be racemized with an alkoxide base [8]. Asymmetric processes to sertraline have been described [26]. Our studies started with the original patented process involving palladium-catalyzed reductive amination of a tetralone to give a mixture of 80% racemic-cis and 20% racemic-trans diastereomers [27]. The cis-diastereomer can be purified by selective crystallization from toluene followed by diastereomeric crystallization of the (lS,4S)-enantiomer using (R)-... 

An award-winning example of green chemistry being used in the redesign of a process is in the production of Pfizer s antidepressant sertraline (see Figure 3.6) (Clark, 2002 Ritter, 2002 US Environmental Protection Agency). 

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