Improved Methodology for the Preparation of Chiral Amines
Improved Methodology for the Preparation of Chiral Amines
Improved Methodology for the Preparation of Chiral Amines
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O<br />
NH 2<br />
1. p-TsOH/toluene<br />
2. BH 3 -THF/THF<br />
HN<br />
1.Column<br />
Chromatograpgy<br />
2.10 mol% Pd-C/EtOH<br />
NH 2<br />
N<br />
OH<br />
N<br />
N<br />
NH 2<br />
S<br />
C<br />
N<br />
NaCN<br />
NC<br />
S<br />
NH<br />
NH<br />
NC<br />
N<br />
H<br />
N<br />
NH<br />
NH 2<br />
CN<br />
CN<br />
CN<br />
Scheme 4.8. Syn<strong>the</strong>sis <strong>of</strong> Namindinil.<br />
4.1.9. Syn<strong>the</strong>sis <strong>of</strong> Ezlopipant:<br />
Ezlopipant is an antiemetic drug which is prescribed <strong>for</strong> severe nausea and vomiting<br />
associated with chemo<strong>the</strong>rapy. [7] <strong>Preparation</strong> starts with <strong>the</strong> condensation <strong>of</strong> acetonitrile with<br />
ester derivative <strong>of</strong> piperidine. Nitrile group is converted to <strong>the</strong> corresponding acid under acid<br />
hydrolysis. The carboxylic acid undergoes spontaneous decarboxylation <strong>for</strong>ming <strong>the</strong><br />
corresponding ketone which is reacted with bromine yielding bromoketone. This unstable<br />
intermediate undergoes spontaneous internal displacement <strong>for</strong>ming quinuclidine (172) as a<br />
quaternary salt. Debenzylation using palladium leads to <strong>the</strong> <strong>for</strong>mation <strong>of</strong> quinuclidone.<br />
Reductive amination 2-methoxy-4-isopropylbenzylamine (174) af<strong>for</strong>ds ezlopipant (175).<br />
89