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Synthesis of ( R )‐3‐( tert ‐Butoxycarbonylamino)‐4‐(2,4,5‐trifluorophenyl)butanoic Acid, a Key Intermediate, and the Formal Synthesis of Sitagliptin Phosphate
Author(s) -
Sreenivasulu Kurella,
Chaudhari Pramod S.,
Achanta Srinivas,
Sud Abhishek,
Dahanukar Vilas,
Cobley Christopher J.,
LlewellynBeard Fiona,
Bandichhor Rakeshwar
Publication year - 2020
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.202000092
Subject(s) - moiety , sitagliptin phosphate , chemistry , sitagliptin , stereoselectivity , yield (engineering) , stereochemistry , phosphate , amino acid , combinatorial chemistry , organic chemistry , catalysis , biochemistry , materials science , medicine , metformin , metallurgy , diabetes mellitus , endocrinology
An alternate formal synthesis of Sitagliptin phosphate is disclosed from 2,4,5‐trifluorobenzadehyde in 8 linear steps with an overall yield of 31%. The chiral β‐amino acid moiety present in sitaglitpin is installed via an asymmetric hydrogenation followed by a stereoselective Hofmann rearrangement as the key steps. The key chiral intermediate Boc‐amino acid 1 prepared by this novel route was further converted to Sitagliptin phosphate following the known literature protocol.