Sertraline chemistry

The reaction of vinylcarbenoids with allylic C-H bonds leads to a remarkable transformation, a combined C-H insertion/Cope rearrangement, which is reminiscent of the tandem cyclopropanation/Cope rearrangement of vinylcarbenoids. An interesting application of this chemistry is the asymmetric synthesis of the antidepressant (-i-)-ser-traline 191 (Scheme 14.26) [134]. The Rh2(S-DOSP)4-catalyzed reaction of the vinyldia-zoacetate 189 with 1,3-cyclohexadiene generates the 1,4-cyclohexadiene 190 in 99% enantiomeric excess. The further conversion of 190 to (-t)-sertraline 191 is then achieved using conventional synthetic transformations. 

Imines readily hydrolyze under basic or acidic conditions. Figure 52 shows the acid-catalyzed hydrolysis of imines. When developing methods to detect imines, it is often necessary to use neutral pH conditions to optimize the stability of the imine. An example of imine formation and hydrolysis is found in the degradation chemistry of the API sertraline hydrochloride (Fig. 53) (86). 

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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