Improved Methodology for the Preparation of Chiral Amines

Reduction of the oxime can be accomplished using a variety of reducing agents. The initial
report employed sodium in methanol for converting the oxime to the target amphetamine.
Other modifications of this approach have been described in recent literatures.
Scheme 4.3.Synthesis of Amphetamine:
The asymmetric synthesis of amphetamines was developed in the seventies of the last
century. The synthesis starts with methyl benzyl which is reductively aminated using readily
available chiral α-methyl benzyl amine producing the imine intermediate and the synthesis is
driven to completion by removing H 2 O with Dean–Stark trap. The resulting imine was
reduced with Raney nickel. The product was isolated and crystallized as HCl salt which is
then hydrogenolyzed with Pd-C producing the primary amine in high overall optical purity.
4.1.4. Synthesis of Sertraline:
Sertraline is an anti-depressant drug that affects serotonin levels in the brain. Initially the
active isomer was not known when both diastereoisomers were prepared through an
unselective route. [3,4] Synthesis starts with Friedel-Crafts reaction between 1,2-
dichlorobenzene and succinic anhydride forming the starting material presented in the
following scheme.
Scheme 4.4. Synthesis of Sertraline:
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